Effect of endotoxins on contractility of smooth muscle preparations from the bovine abomasal antrum

The effects of endotoxin (ET) on spontaneous contractility and of carbachol- and alpha-methyl-5-hydroxytryptamine-(alpha-M-5-HT; 5-HT2 receptor agonist) induced contractions of smooth muscle preparations from the bovine abomasal antrum were investigated in vitro. Preparations from the abomasal antrum of freshly slaughtered healthy dairy cows were cut parallel to the longitudinal and circular fibres, suspended in isolated organ baths, and contractility was recorded and analyzed, using digitalized data. The traits maximum amplitude, time till maximum amplitude, frequency, basal tone, and area under curve were calculated. The contractile effect of Carbachol (CH) was concentration dependent. Repeated administration of CH (3.75 x 10(-6) M), each time interrupted by flushing of the organ baths, did not reveal any significant effect on contractility traits of CH-induced contractions. Endotoxin (10 micrograms/ml; lipopolysaccharide from E. coli, O26:B6) significantly reduced some of the spontaneously occurring contractility traits and of carbachol-(3.75 x 10(-6) M) and alpha-M-5-HT-induced (2.14 x 10(-5) M) contractions. The effects of higher and lower concentrations of ET occurred less consistently. The inhibitory effect of endotoxin was more pronounced after 6 hours as compared to 2 hours of incubation. The results of the present study (i) support the hypothesis of a possible role of endotoxin in reducing motility of the abomasum during the development of spontaneous abomasal displacement in dairy cows, and (ii) may serve as the basis for the development of an in vitro model of abomasal displacement with endotoxemia for future studies on the effect of motility modulating drugs.     

5-Hydroxytryptamine potentiates contraction mediated by the intramural cholinergic nerve in the longitudinal smooth muscle of the ruminant forestomach

The effects of 5-hydroxytryptamine (5-HT) on the longitudinal smooth muscle from the rumen and reticulum of the bovine forestomach were investigated. 5-HT (0.25–490 μM) caused a contraction and a relaxation of the ruminal strips while it produced only an excitatory effect on the reticular strips. These effects were not affected by tetrodotoxin, hexamethonium, atropine or morphine, but were blocked by methysergide, LSD-25 or phenoxybenzamine. 5-HT potentiated the contraction evoked by stimulation of the intramural cholinergic nerves but did not show any effect on the relaxation produced by the non-adrenergic inhibitory nerves' excitation. The 5-HT-induced potentiation was not affected by morphine, LSD-25, methysergide and hexamethonium or high concentration of nicotine. Nicotine and dimethylphenylpiperazinium also caused a transient augmentation of the nerve-mediated contraction, but these effects were abolished by the competitive ganglionic blockers. The evoked contraction was depressed in high-Mg²⁺ solution, but this depression was antagonized partly by 5-HT. The affinity of the cholinomimetics to post-synaptic muscarinic receptor was not affected by 5-HT. It is concluded that contractions or relaxations of bovine forestomach strips induced by 5-HT are mediated through activation of D-receptors in the smooth muscle, and the 5-HT-induced potentiation of the evoked contraction may be elicited through presynaptic neural effects of 5-HT on the cholinergic nerves.     

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.     

5-Hydroxytryptamine mediated contractions in isolated preparations of equine ileum and pelvic flexure: pharmacological characterization of a new 5-HT(4) agonist

The effects of 5-hydroxytryptamine (5-HT), HTF 919, a new 5-HT(4) agonist, and the antagonists SB 203-186 (5-HT(4)) and tropisetron (5-HT(3)) on intestinal motility were tested in vitro on isolated preparations of horse ileum and pelvic flexure. Concentration-response curves were created by cumulative application of the agonists with or without preincubation of the antagonists. The 5-HT preparation induced a concentration-dependent contraction in equine ileum and pelvic flexure. The results indicate that 5-HT receptors are present in all parts of equine intestine investigated in this study. Tropisetron was found to act as a noncompetitive antagonist in all locations of the equine intestine. SB 203-106 was confirmed as an antagonist to 5-HT in the equine ileum circular muscle, in pelvic flexure circular and longitudinal muscle. Nevertheless, a discernible increase of smooth muscle contractions caused by HTF 919 could only be observed in pelvic flexure. In accordance with an earlier study in the guinea pig, in the equine gut HTF 919 acted as a partial agonist for the 5-HT(4) receptor with an affinity constant in the nanomolar range. It is concluded that 5-HT receptors, and especially their subtypes, may represent a promising target for the treatment and prevention of gastrointestinal (GI) motility disorders in horses.     

Effect of orally administered cimetidine and ranitidine on abomasal luminal pH in clinically normal milk-fed calves

OBJECTIVE: To characterize the change of pH in the abomasal lumen throughout a 24-hour period, to determine whether pH of the abomasal body differs from pH of the pyloric antrum, and to determine whether oral administration of cimetidine and ranitidine alters pH of the abomasal lumen in milk-fed calves. ANIMALS: 5 male dairy calves (4 Holsteins-Friesian, 1 Ayrshire), 5 to 15 days old. PROCEDURE: Cannulas were surgically positioned in the abomasal body and pyloric antrum of each calf. Calves received the following treatments in a randomized crossover design: milk replacer (60 ml/kg of body weight, q 12 h [untreated control calves]), milk replacer and cimetidine (50 or 100 mg/kg, q 8 h), or milk replacer and ranitidine (10 or 50 mg/kg, q 8 h). The pH of the abomasal body and pyloric antrum was measured for 24 hours, using miniature glass pH electrodes. RESULTS: Suckling of milk replacer immediately increased abomasal luminal pH from 1.4 to 6.0, followed by a gradual decrease to preprandial values by 6 hours. Preprandial and postprandial pH values were not significantly different between the abomasal body and pyloric antrum, indicating lack of pH compartmentalization in the abomasum of milk-fed calves. Administration of cimetidine and ranitidine caused a significant dose-dependent increase in mean 24-hour abomasal luminal pH. CONCLUSIONS AND CLINICAL RELEVANCE: Abomasal acid secretion in milk-fed calves is mediated in part by histamine type-2 receptors. Cimetidine and ranitidine may be efficacious in the treatment of abomasal ulcers in milk-fed calves.     

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.     

Complex interaction of ergovaline with 5-HT2A, 5-HT1B/1D, and alpha1 receptors in isolated arteries of rat and guinea pig

Vascular effects of ergovaline mediated by 5-hydroxytryptamine(HT)2A, 5-HT1B/1D, and alpha1 receptors were studied in isolated arterial preparations of rat and guinea pig. In rat tail artery ergovaline behaved as a potent contractile partial agonist showing an agonist potency (pEC50) of 8.86 +/- 0.03, a maximum response (Emax) of 59 +/- 2% with respect to 5-HT, and a partial agonist affinity (pK(P)) of 8.51 +/- 0.06. Ergovaline was equipotent with ergotamine (pEC50, 8.69 +/- 0.07; Emax, 52 +/- 4%; pK(P), 8.36 +/- 0.11). Contractile responses to ergovaline and ergotamine were surmountably antagonized by the 5-HT2A receptor antagonist ketanserin (3 nM). Antagonist affinity (apparent pA2) for ketanserin against ergovaline and ergotamine was 9.19 +/- 0.08 and 9.36 +/- 0.17, respectively. Ergovaline showed extremely slow on-set and off-set kinetics in rat tail artery. The construction of cumulative concentration-response curves required about 4 h, and the contractile response to ergovaline (30 nM), which completely abolished the subsequent contractile response to 5-HT (10 nM to 1 mM), could not be reversed by wash-out. In guinea pig iliac artery moderately precontracted with prostaglandin F2alpha (0.05 to 0.5 microM) ergovaline behaved as an agonist (pEC50, 7.71 +/- 0.10) with a potency similar to that of 5-HT (pEC50, 7.60 +/- 0.05). The contractile response to ergovaline was inhibited by the 5-HT1B/1D receptor antagonist GR127935 (10 nM). The apparent pA2 value for GR127935 against ergovaline was 8.90 +/- 0.12. Ergovaline (10 nM) produced no contractile response in guinea pig iliac artery when added before the PGF2alpha-induced precontraction but caused insurmountable blockade of the contractile response to the 5-HT1B/1D receptor agonist 5-carboxamidotryptamine (5-CT). The apparent pA2 value for ergovaline against 5-CT was 8.56 +/- 0.18. In rat thoracic aorta ergovaline (2 microM) activated alpha1 adrenoceptors only with low efficacy (Emax, 12 +/- 3%) but surmountably antagonized norepinephrine-induced contractions with a pK(P) of 7.07 +/- 0.12. It is concluded that the powerful constrictor effect of ergovaline mediated by activation of vascular 5-HT2A and 5-HT1B/1D receptors may explain the vascular symptoms of fescue toxicosis observed in livestock grazing tall fescue pastures infected with the endophytic fungus Neotyphodium coenophialum.     

In vitro effects of cisapride, metoclopramide and bethanechol on smooth muscle preparations from abomasal antrum and duodenum of dairy cows

The objective of this study was to investigate the effects of cisapride (CIS), metoclopramide (MET) and bethanechol (BET) on contractility parameters from smooth muscle preparations of the abomasal antrum and proximal duodenum of cows. Smooth muscle preparations were harvested shortly post-mortem from 42 healthy dairy cows, and concentration-response curves were performed by cumulative application of the drugs. Cisapride and MET did not have any significant effect on the contractility parameters studied, while BET induced a significant, concentration-dependent increase in basal tone (BT), mean amplitude (Amean), and area under the curve (AUC) in smooth muscle preparations from the abomasal antrum, but not from the duodenum. The effect of BET on BT was more pronounced in specimens with longitudinal orientation while the maximal obtainable effect (Vm) in Amean was more pronounced in circular-oriented preparations. Atropine (1 x 10-5 m) significantly inhibited the effect of BET, whereas pre-incubation with hexamethonium or tetrodotoxin (TTX) had no effect, suggesting that the effect was mediated by cholinergic receptors on the smooth muscle. The results may be relevant to diseases or disorders associated with gastric emptying and gastric hypomotility. Further investigations are warranted to investigate the potential ability of BET to enhance abomasal emptying of adult dairy cows.     

Electrophysiological characteristics of tension receptors in the abomasal antrum of sheep

Unitary impulse activity from tension receptors in the abomasal antrum in sheep anaesthetized with chloralose was studied with concurrent measurements of isometric tension in the antral wall, intraluminal pressures and electromyography (EMG). Rhythmical background activity had a close correlation with intraluminal pressure changes and usually a close correlation with local increases in EMG activity and isometric tension. Impulse frequencies increased, but were not sustained, following changes from isotonic to isometric conditions. Tension receptors were excited by transmural compression, by antral distension and by local intra-arterial injections of acetylcholine (2.5–25 µg), pentagastrin (10–20 µg), 5-hydroxytryptamine (1–20 µg), adrenaline (10 µg) cholecystokinin-8 (1–5 µg) or bradykinin (0.5–20 µg), and by systemic injections of bethanecol (5–1000 µg). Local intra-arterial perfusions of atropine (50 µg) and hexamethonium (100 µg) did not abolish spontaneous antral movements or affect the enhanced impulse activity evoked by acetylcholine or 5-hydroxytryptamine. Most antral tension receptors were excited by increases in antral tension or passive distension; they therefore functioned in series with the muscularis externa. The discharges of three tension receptors were off-loaded early during the contraction evoked by local injections of pentagastrin (10–20 µg).Abbreviations b-t balloon-tipped - EMG electromyography - IMP impulse - TTL transistor-transistor logic On study leave from University of Massey, Palmerston North, New Zealand     

The vascular responses of the isolated perfused bovine external ear to exogenous histamine and 5-HT (serotonin)

The responses of the vasculature of isolated, non-sensitized, bovine external ears to histamine and serotonin (5-HT) were evaluated while they were being perfused with Krebs-Henseleit solution, Histamine (10^–5 mol/L to 5×10^–3 mol/L) and 5-hydroxytryptamine (5-HT) (10^–9 mol/L to 10^–2 mol/L) caused increased vascular resistance. Mepyramine (10^–7 mol/L), cimetidine (10^–5 mol/L) and atropine (10^–6 mol/L) inhibited the responses to histamine. The responses to 5-HT were inhibited by methysergide (10^–9 mol/L) and potentiated by morphine (10^–5 mol/L). These results suggest the presence of H₁ and H₂ histamine, and 5-HT receptors in bovine auricular vessels, all of which cause net vasoconstriction.     

5-羟色氨调控动物采食的研究进展

关于5-羟色氨(5-HT)对采食量的影响已有几十年的研究历史。机体内的5-HT主要是以必需氨基酸色氨酸(Trp)作为前体物,在大脑和肠道中合成,并在机体中发挥重要的作用。5-HT无法直接透过血-脑屏障,因此中枢神经系统和外周5-HT作为两个相对独立的系统各自发挥作用。目前,已有大量的研究表明中枢5-HT的多种受体以不同的方式调控动物采食,主要有5-HT1A、5-HT1B、5-HT2A、5-HT2C、5-HT3A、5-HT4、5-HT5A、5-HT6和5-HT7。例如,现在临床上被批准使用的抗肥胖药物氯卡色林就是一种5-HT2C受体激动剂。此外,中枢5-HT还可以协同胰高血糖素样肽-1、饥饿素和胆囊收缩素等外周激素共同调控动物采食行为。外周5-HT也能够通过介导胰高血糖素样肽-1和胆囊收缩素来诱导饱腹感。畜禽生产中主要通过在饲料中添加Trp来增加动物体内5-HT的合成。但目前对于Trp对畜禽采食量的调控机制的研究尚不完善,且有研究表明,不同浓度的Trp对动物采食量的影响不同,不同畜禽饲料中最适Trp的浓度也不同。而Trp主要是通过其代谢产物5-HT来调控动物采食。作者查阅了大量国内外最新的研究成果,从中枢和外周两个途径对5-HT调控动物采食行为的研究进展作一综述,期望通过对Trp的代谢产物5-HT对动物采食调控机制的探讨,为Trp在畜禽生产中的应用提供一定的理论依据。     

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.     

Pharmacological characterisation of the electrically evoked release of monoamines from chicken brain in vitro

1. A study was conducted to develop an in vitro model for examining the basal and electrical-stimulation-induced release of [3H]monoamines from chicken hyperstriatal neurones in order to demonstrate the presence of presynaptic autoreceptors for the three main monoamine transmitters: noradrenaline, dopamine and 5-HT. 2. Two sets of experiments were carried out: the first was to evaluate the effect of calcium and tetrodotoxin (TTX, sodium channel conductance inhibitor) in order to demonstrate that evoked release of monoamines was a consequence of exocytotic processes; the second to investigate the effect of selective agonists and antagonists on neurotransmitter release. 3. Ross and Cobb broiler chickens of either sex (approximately 7 to 8 weeks old) were used. Slices of hyperstriatal tissue were preincubated with [3H]noradrenaline, [3H]dopamine or [3H]5-hydroxytryptamine (5-HT), washed, perfused and electrically stimulated at three time points (S1, S2 and S3) which released [3H]noradrenaline, [3H]dopamine and [3H]5-HT, as determined by scintillation spectrometry. 4. When calcium was removed from, or TTX added to, the superfusion medium prior to and including the second period of electrical stimulation (S2) the evoked releases of [3H]noradrenaline, [3H]dopamine and [3H]5-HT at S2 were abolished. 5. In the presence of the selective alpha2-adrenoceptor agonist UK 14304 during the S2 period, the S2/S1 ratio was lower than the control ratio due to a reduction in the stimulated release of [3H]noradrenaline. The selective alpha2-adrenoceptor antagonist RX 821002 blocked the UK 14304-induced reduction of evoked release and the S2/S1 ratio was similar to the control ratio. 6. The D2-like receptor agonist quinpirole reduced the S2/S1 ratio for [3H]dopamine release, an effect blocked by the antagonist AJ 76. The 5-HT1B receptor agonist CP 94253 during S2 reduced the S2/S1 ratio due to a reduction in evoked [3H]5-HT. This effect was blocked by the 5-HT1B receptor antagonist GR 55562. 7. The results demonstrate, for the first time, the functional presence of presynaptic alpha2-adrenoceptors, presynaptic 5-HT1B autoreceptors and presynaptic D2-like autoreceptors in broiler chicken hyperstriatal neurones in vitro.     

Cardiovascular response to intravenous administration of 5-hydroxytryptamine after type-2 receptor blockade, by metrenperone, in healthy calves

The cardiovascular response to 5-hydroxytryptamine (5-HT) challenge has been previously described in cattle. Abrupt bradycardia, followed by tachycardia, triphasic systemic blood pressure response, and pulmonary hypertension were the major changes elicited by 5-HT. The purpose of the present study was to determine whether the cardiovascular response to 5-HT in calves was attributable to 5-HT2 receptors. A specific 5-HT2 antagonist (metrenperone, 0.05 mg/kg) was administered intramuscular to six unsedated Friesian calves 30 min before the animals were given a 5-min intravenous 5-HT infusion. Mean systemic arterial (SAP), mean pulmonary arterial (PAP), pulmonary capillary wedge (PW) pressures were obtained by means of fluid-filled catheters, and cardiac output (CO) was measured by the thermodilution technique. Heart rate, stroke volume, systemic (SVR) and pulmonary (PVR) vascular resistances were calculated. Administration of 5-HT after metrenperone induced a short-lasting period of severe bradycardia followed by tachycardia and increased CO. The systemic blood pressure response was exclusively hypotensive and associated with a decrease in SVR. Conversely, PAP, PW, and PVR were not modified by 5-HT administration. The results establish that 5-HT induced systemic as well as pulmonary hypertension is mediated through the activation of type-2 serotonergic or alpha-adrenergic receptors, or both. In contrast, neither apnoea, bradycardia and hypotension, nor the positive chronotropic effect induced by 5-HT in cattle are mediated through such receptors.     

Serotonergic signals enhanced hamster sperm hyperactivation

In the present study, we investigated the regulatory mechanisms underlying sperm hyperactivation enhanced by 5-hydroxytryptamine (5-HT) in hamsters. First, we examined the types of 5-HT receptors that regulate hyperactivation. Hyperactivation was significantly enhanced by 5-HT_2A and 5-HT₄ receptor agonists. Moreover, the results of the motility assay revealed that 5-HT_2A, 5-HT₃, and 5-HT₄ receptor agonists significantly decreased the velocity and/or amplitude of sperm. Under 5-HT₂ receptor stimulation, hyperactivation was associated with phospholipase C (PLC), inositol 1,4,5-trisphosphate (IP₃) receptor, soluble adenylate cyclase (sAC), and protein kinase A (PKA). In contrast, under 5-HT₄ receptor stimulation, hyperactivation was associated with transmembrane adenylate cyclase (tmAC), sAC, PKA, and CatSper channels. Accordingly, under the condition that sperm are hyperactivated, 5-HT likely stimulates PLC/IP₃ receptor signals via the 5-HT_2A receptor and tmAC/PKA/CatSper channel signals via the 5-HT₄ receptor. After sAC and PKA are activated by these stimulations, sperm hyperactivation is enhanced.     

Effect of intravenous and aerosol administration of 5-hydroxytryptamine on pulmonary function values in healthy calves.

Effects of IV and aerosol administration of 5-hydroxytryptamine (5-HT) on ventilation, pulmonary mechanics values, pulmonary arterial pressure, and heart rate were investigated in healthy unsedated Friesian calves. Minute volume increased significantly, mainly because of an increase in respiratory rate. Except for total pulmonary resistance after bolus injection, continuous administration of 5-HT given by either route caused significant alterations of lung dynamic compliance and total pulmonary resistance, the former decreasing to one-fifth of its baseline value and the latter increasing twofold. Pulmonary arterial pressure increased significantly, whatever the speed or route of administration. Administration of a bolus did not affect heart rate, whereas continuous IV administration of 5-HT as well by perfusion or by aerosol resulted in sustained tachycardia. It was concluded that 5-HT induces reversible bronchoconstriction and pulmonary vasoconstriction in healthy unsedated calves, 5-HT-induced functional alterations depend on the speed of administration, and excess of 5-HT production or depression in uptake by the lungs during bovine respiratory tract diseases could contribute to pulmonary dysfunction.     

Distribution of muscarinic receptor subtypes and interstitial cells of Cajal in the gastrointestinal tract of healthy dairy cows

OBJECTIVE: To describe the distribution of muscarinic receptor subtypes M(1) to M(5) and interstitial cells of Cajal (ICCs) in the gastrointestinal tract of healthy dairy cows. SAMPLE POPULATION: Full-thickness samples were collected from the fundus, corpus, and pyloric part of the abomasum and from the duodenum, ileum, cecum, proximal loop of the ascending colon, and both external loops of the spiral colon of 5 healthy dairy cows after slaughter. PROCEDURES: Samples were fixed in paraformaldehyde and embedded in paraffin. Muscarinic receptor subtypes and ICCs were identified by immunohistochemical analysis. RESULTS: Staining for M(1) receptors was found in the submucosal plexus and myenteric plexus. Antibodies against M(2) receptors stained nuclei of smooth muscle cells only. Evidence of M(3) receptors was found in the lamina propria, in intramuscular neuronal terminals, on intermuscular nerve fibers, and on myocytes of microvessels. There was no staining for M(4) receptors. Staining for M(5) receptors was evident in the myocytes of microvessels and in smooth muscle cells. The ICCs were detected in the myenteric plexus and within smooth muscle layers. Distribution among locations of the bovine gastrointestinal tract did not differ for muscarinic receptor subtypes or ICCs. CONCLUSIONS AND CLINICAL RELEVANCE: The broad distribution of M(1), M(3), M(5), and ICCs in the bovine gastrointestinal tract indicated that these components are likely to play an important role in the regulation of gastrointestinal tract motility in healthy dairy cows. Muscarinic receptors and ICCs may be implicated in the pathogenesis of motility disorders, such as abomasal displacement and cecal dilatation-dislocation.