Expression and function of 5-HT7 receptors in smooth muscle preparations from equine duodenum, ileum, and pelvic flexure

In horses, gastrointestinal (GI) disorders occur frequently and cause a considerable demand for efficient medication. 5-Hydroxytryptamine receptors (5-HT) have been reported to be involved in GI tract motility and thus, are potential targets for treating functional bowel disorders. Our studies extend current knowledge on the 5-HT₇ receptor in equine duodenum, ileum and pelvic flexure by studying its expression throughout the intestine and its role in modulating contractility in vitro by immunofluorescence and organ bath experiments, respectively.5-HT₇ immunoreactivity was demonstrated in both smooth muscle layers, particularly in the circular one, and within the myenteric plexus. Interstitial cells of Cajal (ICC), identified by c-Kit labeling, show a staining pattern similar to that of 5-HT₇ immunoreactivity.The selective 5-HT₇ receptor antagonist SB-269970 increased the amplitude of contractions in spontaneous contracting specimens of the ileum and in electrical field-stimulated specimens of the pelvic flexure concentration-dependently.Our in vitro experiments suggest an involvement of the 5-HT₇ receptor subtype in contractility of equine intestine. While the 5-HT₇ receptor has been established to be constitutively active and inhibits smooth muscle contractility, our experiments demonstrate an increase in contractility by the 5-HT₇ receptor ligand SB-269970, suggesting it exerting inverse agonist properties.     

Contractile effects of 5-hydroxytryptamine (5-HT) in the equine jejunum circular muscle: functional and immunohistochemical identification of a 5-HT1A-like receptor

REASONS FOR PERFORMING STUDY: Prokinetic drugs used to treat gastrointestinal ileus in man have equivocal results in horses. In man, prokinetic drugs have 5-hydroxytryptamine4(5-HT4) receptors as their target, but little is known about the 5-HT-receptor subtypes in the equine small intestine. OBJECTIVE: Functional and immunohistochemical identification of the serotonin receptor subtype(s) responsible for the 5-HT induced contractile response in the equine circular jejunum. METHODS: Isometric organ-bath recordings were carried out to assess spontaneous and drug-evoked contractile activity of equine circular jejunum. Histological investigations by immunofluorescence analyses were performed to check for presence and localisation of this functionally identified 5-HT receptor subtype. RESULTS: Tonic contractions were induced by 5-HT in horse jejunal circular muscle. Tetrodotoxin, atropine and NG-nitro L-arginine did not modify this response. A set of 5-HT receptor subtype selective antagonists excluded interaction with 5-HT1B, 1D, 2A, 3, 4 and 7 receptors. The selective 5-HT1A receptor antagonists WAY 100635 and NAN 190 caused a clear rightward shift of the concentration-response curve to 5-HT. The contractile effect of 5-CT, that can interact with 5-HT1A, 1B, 1D, 5 and 7 receptors was also antagonised by WAY 100635, identifying the targeted 5-HT receptor as a 5-HT1A-like receptor. Immunohistology performed with rabbit polyclonal anti-5-HT1A receptor antibodies confirmed the presence of muscular 5-HT1A receptors in the muscularis mucosae, and both longitudinal and circular smooth muscle layers of the equine jejunum. CONCLUSIONS: Contractile responses in equine jejunal circular smooth muscle induced by 5-HT involves 5-HT1A-like receptors.     

In vitro evaluation of the effect of the opioid antagonist N-methylnaltrexone on motility of the equine jejunum and pelvic flexure

REASONS FOR PERFORMING STUDY: Although potent analgesics, opioids decrease intestinal activity, leading to ileus in many species. N-methylnaltrexone (MNTX), an opioid antagonist which does not cross the blood-brain barrier and antagonises the morphine effect on the intestine, directly stimulates motility and restores function without affecting analgesic properties. While its use has been reported in human subjects, there is no information with regard to its usage in the horse. OBJECTIVES: To determine whether MNTX has an effect on contractile activity of the equine jejunum and pelvic flexure. METHODS: Using circular smooth muscle strips obtained from 8 mature horses, increasing concentrations of MNTX were added to tissue baths in the range of 1 x 10(-9) to 1 x 10(-5) mol/l, and contractile responses were recorded for 3 mins. Data were analysed using a repeated measures ANOVA to determine whether there was a significant drug effect compared to baseline activity. Data were analysed between the jejunum and pelvic flexure using a Mann-Whitney U test. Statistical significance was established as P < 0.05. RESULTS: The administration of MNTX significantly increased the contractile frequency and amplitude at all concentrations relative to baseline (P < 0.0001) for the jejunum. The response was greatest at 1 x 10(-7) mol/l (P = 0.0005), with a mean difference from baseline of 115.12 g/cm2. The highest concentration evaluated (1 x 10(-5) mol/l) had a mean contractile strength of 69.76 g/cm2, which was significantly greater than baseline activity (P = 0.04). A significant increase in contractile activity for the colon was detected at 3 x 10(-7) mol/l and all subsequent concentrations (P < 0.04). Unlike the jejunum, the contractile activity of the pelvic flexure increased progressively with the addition of each subsequent concentration. CONCLUSIONS: N-methylnaltrexone has a direct effect on circular smooth muscle of the equine jejunum and pelvic flexure resulting in an increase in contractile activity. POTENTIAL RELEVANCE: N-methylnaltrexone could potentially be used in conjunction with morphine to provide potent and effective analgesia without compromising intestinal function. Further in vivo investigations are required to determine whether this agent antagonises morphine's effect on motility.     

Tegaserod (HTF 919) stimulates gut motility in normal horses

REASONS FOR PERFORMING STUDY: It has been shown that the selective 5-HT4 receptor agonist tegaserod induces an increase in frequency and amplitude of contractions in isolated muscle preparations of equine ileum and pelvic flexure. OBJECTIVES: To investigate the effects of tegaserod on gut motility and transit of spheres in normal horses. METHODS: Six mature Freiberger horses were kept under standardised conditions. Effects of tegaserod (0.02 mg/kg bwt i.v. b.i.d. for 2 days) or vehicle on intestinal transit of barium-filled spheres, defaecation and gut sounds were studied in a cross-over design. Spheres were given via stomach tube prior to the first dosing of tegaserod or vehicle. Faeces were collected every 3 h and spheres eliminated were identified radiologically in the faeces. RESULTS: Tegaserod significantly accelerated the gastrointestinal (GI) transit time of spheres and increased the frequency of defaecation and scores of gut sounds compared to vehicle. The compound was well tolerated; no effects on behaviour, body temperature, heart rate, respiratory rate and clinical laboratory data were observed. CONCLUSIONS: Tegaserod efficaciously stimulated motility and accelerate GI transit in healthy horses. POTENTIAL RELEVANCE: Tegaserod may offer therapeutic potential in horses suffering from impaction or paralytic ileus.     

In vitro effects of bethanechol on equine gastrointestinal contractility and functional characterization of involved muscarinic receptor subtypes

The goal of this study was to investigate the effect of bethanechol (BeCh) on contractility patterns of smooth muscle preparations of equine duodenum descendens, jejunum, caecum and pelvic flexure in vitro. Concentration-response relationships were developed for BeCh using in vitro assays with and without preincubation of muscarinic (M) receptor antagonists for M2 and M3 receptors. BeCh induced a significant, concentration-dependent increase in contractile response in equine intestine in specimens with circular orientation. The maximal effect was largest for jejunal specimens with no difference in EC50 within the different locations investigated. The M2 antagonist, AF-DX 116, caused a rightward shift of the concentration-response curve and the M3 antagonist, 4-DAMP (1,1-dimethyl-4-diphenylacetoxypiperidinium iodide), almost completely inhibited the effect of BeCh over the entire concentration-response curve. These data provide evidence that, although the effect of BeCh is predominantly mediated by M3 receptors, M2 muscarinic receptors also play a role in BeCh-induced contraction in specimens of equine intestine. The involvement of other muscarinic receptor subtypes cannot be excluded. Further studies are necessary to understand the effect of BeCh in vivo including diseased animals.     

Pharmacokinetics and in vitro effects of tegaserod, a serotonin 5-hydroxytryptamine 4 (5-HT4) receptor agonist with prokinetic activity in horses

Tegaserod, a serotonin agonist, has been shown to have prokinetic effects in horses, but pharmacokinetic information is not currently available. The pharmacokinetics and in vitro effects of tegaserod were evaluated. Tegaserod increased the contractile activity of smooth muscle preparations of the equine pelvic flexure. Pertinent pharmacokinetic parameters for a single IV and oral dose were determined. Therapeutic plasma concentrations of tegaserod were achieved by a single oral dose at 0.27 mg/kg. These findings indicate that further clinical studies are warranted to investigate potential benefits in cases of functional gastrointestinal motility disorders in horses.     

In vitro investigation of the effect of prostaglandins and nonsteroidal anti-inflammatory drugs on contractile activity of the equine smooth muscle of the dorsal colon, ventral colon, and pelvic flexure

OBJECTIVES: To determine the in vitro effect of prostaglandin E2 (PGE2), PGF2alpha, PGI2; and nonsteroidal anti-inflammatory drugs (NSAID; ie, flunixin meglumine, ketoprofen, carprofen, and phenylbutazone) on contractile activity of the equine dorsal colon, ventral colon, and pelvic flexure circular and longitudinal smooth muscle. ANIMALS: 26 healthy horses. PROCEDURE: Tissue collected from the ventral colon, dorsal colon, and pelvic flexure was cut into strips and mounted in a tissue bath system where contractile strength was determined. Incremental doses of PGE2, PGF2alpha,, PGI2, flunixin meglumine, carprofen, ketoprofen, and phenylbutazone were added to the baths, and the contractile activity was recorded for each location and orientation of smooth muscle. RESULTS: In substance P-stimulated tissues, PGE2 and PGF2alpha enhanced contractility in the longitudinal smooth muscle with a decrease or no effect on circular smooth muscle activity. Prostaglandin I2 inhibited the circular smooth muscle response with no effect on the longitudinal muscle. The activity of NSAID was predominantly inhibitory regardless of location or muscle orientation. CONCLUSIONS AND CLINICAL RELEVANCE: In the equine large intestine, exogenous prostaglandins had a variable effect on contractile activity, depending on the location in the colon and orientation of the smooth muscle. The administration of NSAID inhibited contractility, with flunixin meglumine generally inducing the most profound inhibition relative to the other NSAID evaluated in substance P-stimulated smooth muscle of the large intestine. The results of this study indicate that prolonged use of NSAID may potentially predispose horses to develop gastrointestinal tract stasis and subsequent impaction.     

Equine coronary artery responds to 5-hydroxytryptamine with relaxation in vitro

Isolated equine coronary arteries responded to 5-hydroxytryptamine (5-HT) with relaxations in both endothelium-dependent and endothelium-independent mechanisms. Experiments were designed to characterize the 5-HT receptor sub type mediating these relaxations. Both 5-HT and alpha-methyl-5-HT (α-Me-5- HT; 5-HT₂ agonist) produced concentration-dependent relaxations in equine coronary arteries precontracted with a thromboxane A₂ derivative (0N011113). The degree of the maximal relaxation induced by α t-Me-5-HT was about one-half of that induced by 5-HT. In the coronary arteries without endothelium, α -Me-5-HT produced no relaxation, but 5-HT caused relaxation, which was inhibited by a 5-HT₁ antagonist (methysergide, mianserin and methiothepin), but was inhibited neither by ketanserin (5-HT₂ antagonist) nor by MDL72222 (5-HT₃ antagonist). In the coronary arteries with endothelium, however, the relaxation induced by α -Me-5-HT was inhibited by ketanserin, L-nitro-arginine (NO synthase inhibitor) and methylene blue (soluble guanylate cyclase inhibitor). These results suggest that the relaxation induced by 5-HT in equine coronary arteries depends mainly on the stimulation of both 5-HTi receptor subtype on smooth muscle cells directly, and 5-HT₂ receptor subtype on endothelial cells indirectly by liberating endothe-lium-derived NO.     

In vitro effects of 5-hydroxytryptamine and cisapride on the circular smooth muscle of the jejunum of horses

OBJECTIVE: To determine effects of cisapride and 5-hydroxytryptamine (5-HT) on the jejunum of horses. SAMPLE POPULATION: Jejunal muscle strips from 8 horses. PROCEDURE: Muscle strips were suspended in isolated muscle baths. Isometric stress responses to 5-HT and cisapride, with and without specific antagonists, were determined. RESULTS: Muscle strips incubated with atropine and tetrodotoxin responded to 5-HT and cisapride with an increase in contractile force. The 5-HT caused a concentration-dependent increase in contractile amplitude, with a maximum response (Emax) of 1,151+/-214 g/cm2 and a molar concentration that induces contractile force equal to 50% of maximum response (EC50) of 0.028+/-0.002 microM. Prior incubation with the 5-HT2 antagonist ketanserin decreased the Emax (626 +/-147 g/cm2) and potency (EC50, 0.307+/-0.105 microM) of 5-HT Prior incubation with the 5-HT3 antagonist tropisetron decreased the efficacy (Emax, 894+/-184 g/cm2) to 5-HT Cisapride also caused a concentration-dependent increase in contractile amplitude, with an Emax of 331+/-82 g/cm2 and an EC50 of 0.302+/-0.122 microM. Prior incubation with ketanserin decreased the Emax (55+/-17 g/cm2) and potency (EC50, 0.520+/-0.274 microM) of cisapride. CONCLUSION AND CLINICAL RELEVANCE: Stimulatory effects of 5-HT and cisapride on circular smooth muscle of equine jejunum are mediated primarily through a noncholinergic effect. The effects of 5-HT are mediated, at least partially, by 5-HT2 and 5-HT3 receptors, whereas the effects of cisapride are mediated primarily by 5-HT2 receptors. This may impact treatment of horses with postoperative ileus.     

In vitro effects of tachykinins on the smooth musculature of horse gut

The contractile effects of the tachykinins eledoisin, substance P and neurokinin A and B were investigated in vitro on circular and longitudinal muscle strips from horse duodenum, ileum and colon. Circular smooth muscle of the small intestine was highly responsive, large intestine circular smooth muscle less so, while longitudinal muscle from all gut segments was much less sensitive. pD₂ values and intrinsic activities on small intestine circular muscle indicated differences in receptor distribution between the duodenum and ileum: NK₃ and a smaller number of NK₂ receptors being present in the duodenum, and NK₂ receptors predominating in the ileum. Notwithstanding this, eledoisin and neurokinin B were the most active substances on duodenum and ileum, respectively. These findings suggest that tachykinins may play a role in equine gastrointestinal pathophysiology.     

Prokinetic effects of erythromycin on the ileum, cecum, and pelvic flexure of horses during the postoperative period

OBJECTIVE: To evaluate the effect of erythromycin on motility of the ileum, cecum, and pelvic flexure of horses during the postoperative and post-recovery periods. ANIMALS: 8 healthy adult horses. PROCEDURE: Horses were anesthetized and bipolar electrodes were implanted in smooth muscle of the ileum, cecum, and pelvic flexure. Approximately 4, 16, and 24 hours (postoperative recording sessions) and at least 8 days (post-recovery recording session) after surgery, myoelectric activity was recorded before and after administration of erythromycin (0.5 mg/kg). RESULTS: Following erythromycin administration, myoelectric activity was increased in the ileum during all postoperative recording sessions but not during the post-recovery recording session. Myoelectric activity was increased in the cecum following erythromycin administration only during the post-recovery recording session. Myoelectric activity was increased in the pelvic flexure following erythromycin administration during all recording sessions. During several recording sessions, there were short periods during which myoelectric activity was significantly decreased following erythromycin administration. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that erythromycin has an effect on myoelectric activity of the ileum, cecum, and pelvic flexure in horses; however, prokinetic effects of erythromycin administered during the postoperative period were not always the same as effects obtained when the drug was administered after horses had recovered from the effects of surgical implantation of recording devices. Therefore, caution must be exercised when extrapolating results of prokinetic studies in healthy animals to animals with abnormal gastrointestinal tract motility.     

Tachykinin receptors in the equine pelvic flexure

Tachykinins, of which substance P (SP) is the prototype, are neuropeptides which are widely distributed in the nervous systems. In the equine gut, SP is present in enteric nerves and is a powerful constrictor of enteric muscle; in other species, SP is also known to have potent vasodilatory and pro-inflammatory effects. The specific effects of SP are determined by the subtype of receptor present in the target tissue. There are 3 known subtypes of tachykinin receptors, distinguished by their relative affinities for SP and other tachykinins. The distribution of SP binding sites in the equine pelvic flexure was determined using 125I-Bolton Hunter SP (I-BHSP) autoradiography. Most I-BHSP binding sites were determined to be saturable and specific, therefore presumably representing tachykinin receptors. The greatest degree of I-BHSP binding occurred over very small vessels, and over the muscularis mucosae; I-BHSP binding was also intense over the circular muscle of the muscularis externa and mucosa, and present, although less intense, over the longitudinal muscle of the muscularis externa. Competition of I-BHSP with specific receptor agonists for binding sites in the equine pelvic flexure were used to determine the subtypes of tachykinin receptors present. The neurokinin-1 receptor subtype predominated in the equine pelvic flexure, followed by the neurokinin-3 receptor subtype.     

Proteinase-activated receptor 2 expression in the intestinal tract of the horse

Proteinase-activated receptor 2 (PAR₂) is a G-protein-coupled receptor for trypsin and mast cell tryptase; it is highly expressed at the intestinal level with multiple functions, such as epithelial permeability and intestinal motility. Many proteases activate PAR₂ during tissue damage, suggesting a role of the inflammatory response receptors. The aim of the study was to evaluate the distribution and expression of PAR₂ in the jejunum, the ileum and the pelvic flexure, using samples collected from healthy adult horses after slaughter. Proteinase-activated receptor 2 immunoreactivity (PAR₂-IR) was observed in the enterocytes, intestinal glands, the smooth muscle of the muscularis mucosae, and the longitudinal and circular muscle layers; there were no differences in the distribution of PAR₂-IR in the different sections of the intestinal tract. The protein expression level showed that the relative amount of the PAR₂ content in the mucosa of the intestinal tract decreased from the small to the large intestine while the PAR₂ mRNA analysed showed similar values. This study provides relevant findings concerning the distribution of the PAR₂ in the intestines of healthy horses and represents the starting point for evaluating the role of the PAR₂ during strangulative intestinal disease and consequent systemic intestinal reperfusion/injury complications in horses in order to identify and employ antagonist PAR₂ molecules.     

In vitro investigation of the effects of cyclooxygenase-2 inhibitors on contractile activity of the equine dorsal and ventral colon

OBJECTIVE: To evaluate the effect of 2 cyclooxygenase (COX)-2 inhibitors on contractile activity of the circular smooth muscle layer of the equine dorsal and ventral colon. SAMPLE POPULATION: Samples of the dorsal and ventral colon obtained from 10 healthy horses. PROCEDURE: Full-thickness tissue samples were collected from the dorsal colon in the area of the diaphragmatic flexure and the ventral colon in the area of the sternal flexure. Samples were cut into strips oriented along the fibers of the circular muscle layer and mounted in a tissue bath system for determination of contractile strength. Incremental amounts of etodolac, nabumetone, and indomethacin were added, and contractile activity was recorded. RESULTS: Response of the dorsal and ventral colon to nonsteroidal anti-inflammatory drugs (NSAIDs) was variable. Indomethacin induced the greatest reduction in contractile activity, followed by nabumetone. For etodolac, the difference from baseline values was only significantly reduced at the highest concentration used (1 X 10(5)M) for the ventral colon. CONCLUSIONS AND CLINICAL RELEVANCE: The NSAIDs that are designed to target the COX-2 isoform appeared to have variable effects on the contractile activity of the equine dorsal and ventral colon. Etodolac appeared to have the least effect on contractile activity, compared with the effects attributable to nabumetone, and would potentially have the fewest adverse effects relative to motility of the dorsal and ventral colon.     

5-Hydroxytryptamine-4 receptor messenger ribonucleic acid levels and densities in gastrointestinal muscle layers from healthy dairy cows

Serotonin (5-hydroxytryptamine, 5-HT) is involved in gastrointestinal tract (GIT) motor functions through binding to specific receptors located in the GIT walls. The objectives of the current study were to compare mRNA levels and binding sites of 5-HT(4) receptors (5-HTR(4)) in smooth muscle layers from the fundus abomasi, pylorus, ileum, cecum, proximal loop of the ascending colon (PLAC), and external loop of the spiral colon (ELSC) of healthy dairy cows, and to verify whether mRNA and protein expression were correlated. Smooth muscle samples were prepared by scraping the mucosa and submucosa from full-thickness intestinal wall samples. The mRNA levels of 5-HTR(4) were measured by real-time PCR and expressed relative to those of the housekeeping gene glyceraldehyde phosphate dehydrogenase. Binding studies were performed using the 5-HTR(4) antagonist [(3)H]GR113808. The mRNA levels of 5-HTR(4) were affected (P < 0.05) by location along the GIT. The mRNA levels of 5-HTR(4) in the ELSC and the ileum were greater than in the PLAC (P = 0.05 and P = 0.07, respectively) but similar to those of all other locations. The competitive binding of [(3)H]GR113808 to suspended membranes from the fundus abomasi, pylorus, cecum, and ELSC was best fit by a 2-site receptor model, whereas it was best fit by a 1-site receptor model in the ileum and PLAC. The mRNA levels and numbers of 5-HTR(4) were not correlated (r = 0.14; P = 0.71). In conclusion, mRNA and binding sites for 5-HTR(4) are present in the smooth muscle layer of the entire GIT of dairy cows and may play a role with respect to motility. The effects of activation of this receptor subtype may be different among GIT locations due to differences in the amount of high- relative to low-affinity binding sites.     

Cholinergic activity of intestinal musclein vitro taken from horses with and without equine grass sickness

Equine grass sickness (EGS) is a pan-dysautonomia of horses that involves central and peripheral neuronal degeneration and ultimately depletion. This is the first reported functional study on the motility of equine intestine taken immediatelypost mortem from horses with EGS. Strips of smooth muscle from the small intestine of healthy and EGS-affected horses were suspended in an organ bath and their motility was measured isometrically. The activity of the cholinergic system was studied. Physostigmine enhanced the motility of all muscle strips. Tissues taken from horses suffering from acute grass sickness (AGS) had the longest latency before a measurable response could be obtained (p<0.05). The ileum appeared to be damaged by EGS to a greater extent than the duodenum. For the duodenal strips the enhanced rate of spontaneous contractions was significant (p<0.05) for both normal tissue and that affected by grass sickness but this was not the case for the ileal strips. Muscarinic receptor sensitivity investigation using bethanecol suggested a hypersensitivity of receptors with AGS material,Abbreviations AGS acute grass sickness - CGS chronic grass sickness - ED₅₀ median effective dose - EGS equine grass sickness - VIP vasoactive intestinal peptide     

Food intake and rumen motility in dwarf goats. Effects of some serotonin receptor agonists and antagonists

The serotonergic regulation of feeding behaviour has not so far been studied in ruminants. Therefore, the effects of some serotonin (5-HT) receptor agonists and antagonists on food intake and forestomach motility were studied in dwarf goats.Goats ate less food when treated intravenously (IV) with the 5-HT precursor 5-HTP (25 µg, 50 µg or 100 µg kg^–1 min^–1 over 15 min) than when they were treated with 5-HT (which does not pass the blood-brain barrier) or with saline. Accordingly, IV dexfenfluramine infusions (50 µg or 100 µg kg^–1 min^–1 over 15 min), which induces release of brain 5-HT, also led to dose-related reductions in food intake. In contrast, no anorectic effects were observed after IV infusions with the selective 5-HT reuptake inhibitor fluoxetine (100 µg kg^–1 min^–1 over 15 min), the selective 5-HT1A agonist 8-OH-DPAT (0.5 µg kg^–1 min^–1 over 15 min), or eltoprazine (4 or 8 µg kg^–1 min^–1 over 15 min), a mixed 5-HT1A/5HT1B receptor agonist. None of the 5-HT antagonists tested gave any increase in food consumption in this model. Interestingly, the non-selective 5-HT receptor antagonist methysergide (360 µg/kg IV) reduced food intake. This effect was most noticeable at 3 h after injection. The 5-HT3 receptor antagonist ondansetron (IV 10 µg kg^–1 min^–1 over 15 min) and the peripheral 5-HT2 receptor antagonist xylamidine (IV 100 µg kg^–1 min^–1 over 10 min) failed to modify food intake. These results provide evidence for central serotonergic involvement in the control of feeding. However, this control system differs markedly in goats and rodents.Dexfenfluramine, 5-HTP and eltoprazine administered at similar dose rates to those used in the food intake experiments induced some clinical signs including inhibition of forestomach contractions. These results, together with our earlierin vivo andin vitro observations, suggest that the inhibitory effects of serotonin receptor agonists on forestomach contractions are due to interactions with both peripheral and central serotonergic receptors. The change in smooth muscle tension, which leads to a change in the signals transmitted via vagal afferents to the central nervous system, appears not to modify feeding behaviour in dwarf goats.     

Effects of α2-adrenergic drugs on small intestinal motility in the horse: An in vitro study

The effects of selective α₂-agonists (xylazine, detomidine and medetomidine) and antagonists (yohimbine and atipamezole) on in vitro small intestine motility in the horse were evaluated. Samples of equine jejunum were placed in isolated organ baths and drug-induced modifications of motility were measured by means of an isotonic transducer. All tested α₂-agonists dose-dependently reduced both spontaneous and electrically-evoked phasic contractions. Conversely, α₂-antagonists were ineffective when tested alone, and showed a heterogeneous and dose-independent ability to inhibit agonist activity. In particular, the antagonism exerted by higher concentrations of both yohimbine and atipamezole against α₂-agonists was weaker than when lower concentrations were used. The data are indicative of the presence of both pre- and post-synaptic α₂-adrenoceptors with inhibitory activity on equine jejunum motility, and support a possible therapeutic utility of these drugs in horse intestinal disorders associated with hypermotility.     

Motility of the distal portion of the jejunum and pelvic flexure in ponies: effects of six drugs

Bipolar stainless steel electrodes were surgically implanted in 4 ponies to record myoelectrical and mechanical activity of the distal portion of the jejunum and pelvic flexure. After determining normal activity, the effects of neostigmine, xylazine, flunixin meglumine, dipyrone, panthenol, and atropine sulfate were determined. Flunixin meglumine, dipyrone, and panthenol had no effect on the motility of the jejunum or pelvic flexure. Xylazine and atropine sulfate decreased motility of the distal portion of the jejunum and pelvic flexure, with atropine sulfate having a greater effect and lasting longer. Neostigmine stimulated propulsive motility in the pelvic flexure only.     

Distribution of the neurokinin-1 receptor in equine intestinal smooth muscle

REASON FOR PERFORMING STUDY: Tachykinins have profound effects on equine intestinal motility, but the distribution of the neurokinin receptors (NKRs) through which they act is unknown. This study reports the distribution of one of these receptors, the neurokinin-1 receptor (NK1R), in smooth muscle throughout the equine intestinal tract. OBJECTIVES: To quantify the distribution of the NK1R, based upon mRNA expression, in smooth muscle of different regions of the equine intestinal tract. METHODS: Nine regions of the intestinal tract were sampled in 5 mature horses. Total RNA was isolated from smooth muscle and reverse transcribed; NK1R mRNA was then quantified using real-time PCR. RESULTS: NK1R mRNA was found at all levels of the sampled intestinal tract. The smooth muscle of the proximal small intestine and the ventral colon exhibited the highest level of NK1R mRNA expression in the equine intestinal tract. CONCLUSIONS: Tachykinins probably affect intestinal contractility and propulsion in the proximal small intestine and in the ventral colon.