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.     

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.     

Estrous cycle-dependent differences in responsiveness to prostaglandins and contractile agents in sheep (Ovis aries) cervical smooth muscle

We investigated the influence of the phase of the estrous cycle on mechanical responses elicited in sheep cervix by potassium chloride (KCl), acetylcholine chloride (ACh), prostaglandin F2 alpha (PGF2 alpha) and prostaglandin E1 (PGE1). The cervix of adult ewes (n = 48) were classified according to the presence or absence of corpora lutea (luteal or follicular phase, respectively). Muscle strips of the circular and longitudinal layers were prepared in an organ bath and coupled to an isometric force transducer. Concentration-response curves were obtained noncumulatively. KCl and ACh produced concentration-dependent contractions in all preparations in both phases of the estrous cycle. However, maximum effect, EC50 and slope values of KCl and ACh were not significantly different between muscle layers, as well as between the phases of the estrous cycle. The prostanoid, PGF2 alpha, produced a significant reduction in the amplitude of spontaneous contractions for all preparations. The depressant effect of PGF2 alpha on spontaneous contractions of circular smooth muscle was significantly greater during the follicular than the luteal phase, whilst the depressant effect of PGF2 alpha on the longitudinal layer did not differ between phases of the estrous cycle. PGE1 significantly reduced the amplitude of spontaneous contractions on circular but not on longitudinal preparations. In conclusion, we have characterized with in vitro preparations of circular and longitudinal muscle layers of ewes during the follicular and luteal phases of the estrous cycle, the parameters of the K- and ACh-induced contractions on cervix and the efficacy of PGF2 alpha and PGE1 on inhibition spontaneous contractile activity.     

In vitro effects of nonsteroidal anti-inflammatory agents and prostaglandins I2, E2, and F2alpha on contractility of taenia of the large colon of horses.

OBJECTIVES: To determine the in vitro effect of various prostaglandins (PG) and nonsteroidal anti-inflammatory drugs (NSAID) on contractile activity of the large-colon taenia of horses. ANIMALS: 14 healthy horses. PROCEDURE: The taenia was collected from the ventral colon, cut into strips (2 X 10 mm), and mounted in a tissue bath system (20-ml capacity) that contained oxygenated Krebs buffer solution warmed to 37.5+/-0.5 C. After equilibration, incremental doses of PGE2, PGF2alpha, PGl2, flunixin meglumine, carprofen, ketoprofen, and phenylbutazone were added to the baths, and contractile activity was recorded. Magnitude of the response was calculated by comparing contractile activity before and after administration of the PG or NSAID to the tissue baths. RESULTS: PGE2 and PGF2alpha, caused a significant increase in contractile activity, whereas PGI2 induced an inhibitory response. Activity of NSAID on contraction was predominantly inhibitory. At low concentrations, ketoprofen induced an excitatory effect, which then became inhibitory at high concentrations. Compared with the other NSAID, carprofen significantly reduced contractile activity at lower concentrations. CONCLUSIONS: PGE2 and PGF2alpha appear to enhance contractility of large-colon taenia of horses, whereas PGI2 was inhibitory in the in vitro model. Administration of NSAID also inhibited contractility, with carprofen having the most potent effect. CLINICAL RELEVANCE: Administration of NSAID in combination with liberation of endogenous PG may predispose horses to development of intestinal stasis and subsequent impaction.     

奶牛输卵管平滑肌前列腺素类受体的分析研究

本研究选用了前列腺素类化合物(Prostaglandin E2（PGE2）、Prostaglandin F2α（PGF2α）、Prostaglandin D2（PGD2)）和受体选择性激动剂（Butaprost、U-46619）,用多道生理信号采集系统测定其对体外分离的奶牛输卵管峡部及壶腹部平滑肌收缩的影响,以此初步揭示受体的种类。结果发现,PGE2和Butaprost均抑制了奶牛输卵管峡部、壶腹部的自发性收缩运动,呈现明显的浓度依存性舒张反应;PGF2α在高浓度(1～10 μmol/L)下,使峡部和壶腹部的自发性收缩运动有了显著增强;PGD2在低浓度时轻微抑制了壶腹部平滑肌的收缩,但在高浓度(1～10 μmol/L)时加强了峡部和壶腹部平滑肌的收缩;U-46619从低浓度便引起了输卵管峡部和壶腹部平滑肌的强烈收缩。结果表明,EP4、EP2、FP、DP和TP受体同时存在于奶牛输卵管平滑肌上,能与内源性前列腺素类结合并参与调节输卵管平滑肌的自发性收缩。     

Adrenergic, cholinergic, and nonadrenergic-noncholinergic intrinsic innervation of the jejunum in horses.

OBJECTIVE: To determine the major neurotransmitters that regulate contractile activity in the jejunum of horses. SAMPLE POPULATION: Jejunal specimens from 65 horses without gastrointestinal tract lesions. PROCEDURE: Jejunal smooth muscle strips, oriented in the plane of the circular or longitudinal muscular layer, were suspended isometrically in muscle baths. Neurotransmitter release was induced by electrical field stimulation (EFS) delivered at 30 and 70 V intensities and at various frequencies on muscle strips maintained at low or high muscle tone. To detect residual nonadrenergic-noncholinergic neurotransmission, the response of muscle to EFS in the presence of adrenergic and cholinergic blockade was compared with the response in the presence of tetrodotoxin. RESULTS: Atropine (ATR) decreased the contractile response of muscle strips to EFS under most conditions. However, ATR increased the contractile response of high-tone circular muscle. Adrenergic blockade generally increased the muscle responses to 30 V EFS and in high-tone longitudinal muscle but decreased contractile responses in high-tone circular muscle. Tetrodotoxin significantly altered the responses to EFS, compared with adrenergic and cholinergic receptor blockade. CONCLUSIONS: Acetylcholine and norepinephrine appear to be important neurotransmitters regulating smooth muscle contractility in the equine jejunum. They induce contraction and relaxation, respectively, in most muscle preparations, although they may cause opposite effects under certain conditions. In addition, nonadrenergic-noncholinergic excitatory and inhibitory influences were detected. CLINICAL RELEVANCE: Acetylcholine or norepinephrine release within the myenteric plexus of horses may alter gastrointestinal motility.     

Pharmacological modulation of postprandial colonic motor activity in the pony

The contractile activity of the equine large intestine exhibited a biphasic response to feeding: enhancement of migrating complexes passing along the colon and an increase of 50% in cyclic variations in smooth muscle at intervals of 20 min on the left ventral colon for a period of 5 to 7 h postfeeding. The cholinergic agonist, bethanechol (50 micrograms/kg subcutaneously), induced both the migrating complexes and the cyclic variations at intervals of 10-15 min. In contrast, the intra-arterial infusion of PGF2 alpha (3 micrograms/kg/min) increased the contractile activity during infusion, but without inducing distinct patterns of activity. Atropine but not indomethacin or flunixin pre-treatment prevented the effects of postprandial, cholinergic and PGF2 alpha stimulation of colonic motility, suggesting that the gastrocolonic reflex involved mainly cholinergic stimulation of the caecum and replicated colon, including the prostaglandin F2 alpha excitatory effects.     

In vitro synthesis of prostaglandin E and F2 alpha by pig endometrium in the presence of estradiol, catechol estrogen and ascorbic acid

These experiments were undertaken to determine the potential for estradiol-17 beta (E2), 2-hydroxyestradiol-17 beta (2-OH-E2) and 4-hydroxyestradiol-17 beta (4-OH-E2) to regulate prostaglandin (PG) E and F2 alpha synthesis by pig endometrium. Endometrium was collected from pigs on d 10 of pregnancy and incubated (15 to 20 mg/well) for three 2-h periods in 2 ml of medium in 24-well culture plates. At the end of each period, the medium was removed and frozen. Later media were thawed and assayed for PGE and PGF2 alpha. During Periods 2 and 3, the medium contained 0, 25, 50, 100 or 150 microM 2-OH-E2 (Exp. 1); 0, 25 or 50 microM 4-OH-E2 (Exp. 2); or 0, 25 or 50 microM E2 (Exp. 3). Each experiment was a factorial with 2-OH-E2, 4-OH-E2 or E2 as one main effect and 0 or 1 mM ascorbate as a second main effect. Ascorbate decreased (P less than .01) PGE and PGF2 alpha release in all experiments. Two-hydroxyestradiol-17 beta decreased (P less than .01) PGE and PGF2 alpha release into the medium during Periods 2 and 3 in a dose-dependent manner (Exp. 1). In Exp. 2, 4-OH-E2 decreased (P less than .07) endometrial release of PGE and PGF2 alpha in Periods 2 and 3 and increased (P less than .01) the PGE:PGF2 alpha in Period 3. In Exp. 3, E2 decreased release of PGE during Period 3 and PGF2 alpha release during Period 2. The PGE:PGF2 alpha was not altered by E2.(ABSTRACT TRUNCATED AT 250 WORDS)     

In vitro effects of erythromycin, lidocaine, and metoclopramide on smooth muscle from the pyloric antrum, proximal portion of the duodenum, and middle portion of the jejunum of horses

OBJECTIVE: To evaluate effects of erythromycin, lidocaine, and metoclopramide on smooth muscle of the pyloric antrum (PA), proximal portion of the duodenum (PD), and middle portion of the jejunum (MJ) of horses. Sample Population-Strips of smooth muscle from 7 horses. PROCEDURE: Isolated muscle strips were suspended in a bath and attached to isometric force transducers. Once stable spontaneous contractions were observed, agents were added. Isometric stress responses were compared with the amplitude of spontaneous contractions. RESULTS: A single dose of erythromycin to the PA increased contractile amplitude (CA) for the longitudinal smooth muscle (mean +/- SEM, 76+/-16 g/cm2) but decreased CA for circular smooth muscle (-79+/-23 g/cm2). The inhibitory effect was decreased by tetrodotoxin, N(G)-nitro-L-arginine methyl ester, and a vasoactive intestinal peptide antagonist. Erythromycin increased CA for the MJ, which was maximal at 10(-4)M (171+/-36 g/cm2). Lidocaine increased CA for the PD, which was maximal at 10(-4) M (60+/-5 g/cm2). Metoclopramide increased the CA, which was maximal at 10(-4) M for the PA (75+/-26 g/cm2), PD (279+/-33 g/cm2), and MJ (456+/-59 g/cm2). CONCLUSIONS: Regional differences in responses to erythromycin, lidocaine, and metoclopramide were evident in the gastrointestinal tract of horses. Metoclopramide increased CA in all tissues used, whereas erythromycin inhibited CA in circular smooth muscle but stimulated CA in longitudinal smooth muscle from the PA. Inhibition is caused by stimulation of inhibitory nerves and is mediated, in part, by nitric oxide and vasoactive intestinal peptide.     

Serum glucocorticoids, growth hormone and insulin and plasma glucose in bulls given prostaglandin E2 or F2 alpha 1.

Plasma glucose and serum insulin, growth hormone and glucocorticoid concentrations were determined in five yearling bulls given (im) 5, 15 or 30 mg prostaglandin E2 (PGE2), 30 mg prostaglandin F2 alpha(PGF2 alpha) or saline. Jugular blood was collected at frequent intervals around the time of injection and at .5--hr intervals from 1 to 9 hr after injections. Thirty milligrams PGE2 and 30 mg PGF2 alpha each caused 15- to 20-fold increases in serum glucocorticoids. Glucocorticoids increased with increasing doses of PGE2. Although PGE2 and PGF2 alpha each increased blood growth hormone, this effect was about twofold larger after PGE2. By contrast, PGE2 depressed serum insulin about 50% for 1 hr, then insulin increased about sixfold until 3 to 4 hours. Blood serum insulin increased after PGF2 alpha, but this effect only approached significance (P less than .10). Plasma glucose increased about 10 mg/100 ml after PGE2, but was not affected significantly by PGF2 alpha. Thus, the effects of PGE2 and PGF2 alpha on hormones which control glucose metabolism differ markedly. We speculate that PGE2 caused a twofold increase in growth hormone secretion within 10 to 20 min, that increased growth hormone induced increased blood glucose within 1 to 2 hr and that increased glucose caused increased insulin secretion at 2 to 4 hr, but we cannot rule out a transitory (1 hr) suppressive effect of PGE2 directly on the pancreas.     

Prostaglandin E2-9-ketoreductase activity of preovulatory ovine follicles

Enhanced accumulation of follicular PGF2 alpha with respect to PGE2 during the later phase of the preovulatory period is an apparent prerequisite for ovulation in sheep. Prostaglandin (PG) E2-9-ketoreductase is the enzyme that converts PGE2 into PGF2 alpha. Expression of activity of this enzyme by tissue homogenates of preovulatory ovine follicles was assessed. Homogenates were incubated in the presence of tritiated PGE2. Prostaglandin F2 alpha (i.e., product) was separated from PGE2 by Sephadex chromatography and quantitated by liquid scintillation counting. Progesterone in follicular fluid was measured by RIA. Follicular activity of PGE2-9-ketoreductase and content of progesterone increased approximately sixfold as the time of ovulation approached. Formation of PGF2 alpha from PGE2 was not influenced by inhibition of follicular synthesis of prostaglandins by indomethacin, nor did such treatment affect follicular production of progesterone. Inhibition of follicular synthesis of progesterone by isoxazol suppressed enzymatic conversion of PGE2 into PGF2 alpha; this effect was reversed by progesterone. It appears that progesterone plays an intrafollicular role in induction of activity of PGE2-9-ketoreductase in sheep.     

Effect of prostaglandin F2 alpha, phenylephrine and ergonovine on uterine contractions in the ewe

Two experiments were conducted to determine the effect of prostaglandin F2 alpha (PGF2 alpha), phenylephrine and ergonovine on uterine contractions. In the first experiment, ewes were bilaterally ovariectomized, and a strain gauge force transducer was sutured to the serosa of one uterine horn. Each ewe was treated sc with 2 micrograms of estradiol-17 beta daily to prevent regression of the uterus. Beginning at least 5 d after ovariectomy, four dose levels of PGF2 alpha, phenylephrine and methoxamine were given by im injection and ergonovine was given by im or iv injection. Phenylephrine, methoxamine and ergonovine are alpha-adrenoceptor agonists. Uterine activity was recorded by physiograph for 30 min before and 90 min after treatment. Tracing were analyzed for 20-min periods before treatment and 4 to 24 min and 50 to 70 min after treatment. In Exp. 2, transducers were attached to uteri of intact ewes at d 10 to 12 of an estrous cycle. During subsequent estrus, one or two dose levels of PGF2 alpha, phenylephrine and ergonovine were given by im injection and uterine activity recorded. In Exp. 1, PGF2 alpha and phenylephrine increased (P less than .05 or .01) the number of amplitude of contractions at both 4 to 24 and 50 to 70 min. Ergonovine given im increased the number of contractions. In intact estrous ewes, PGF2 alpha increased the number and amplitude of contractions at 4 to 24 min, phenylephrine increased the number and amplitude at both 4 to 24 and 50 to 70 min, and ergonovine increased the number slightly but significantly at 4 to 24 min.(ABSTRACT TRUNCATED AT 250 WORDS)     

Prostaglandin F2 alpha-induced response of the bovine ovary, oviduct (uterine tube), and uterus

Tissue strips from the ovary, (uterine tube), and oviduct, and uterus of pregnant and nonpregnant cows were tested for their contractile response to prostaglandin F2 alpha (PGF2 alpha). When 2.1 x 10(-6)M PGF2 alpha was added to the uterine strips, tension of tissues from pregnant cows increased sharply; however, tension in tissues from nonpregnant cows only increased moderately. Similar concentrations failed to elicit any response from oviductal tissues of either group. Unlike the uterus and the oviduct, the ovaries contracted slowly and irregularly. They responded with varying degrees of stimulation; ovaries from pregnant cows with brief and mild stimulation and ovaries from nonpregnant cows with slower and relatively stronger stimulation. Results indicate that the bovine ovary contracts rhythmically and that its sensitivity to PGF2 alpha decreases during pregnancy in contrast to the bovine uterus which becomes increasingly sensitive during pregnancy.     

Evaluation of nitric oxide as an inhibitory neurotransmitter in the equine ventral colon

OBJECTIVE: To determine the role of nitric oxide and an apamin-sensitive nonadrenergic noncholingeric inhibitory transmitter on contractility of the ventral colon of horses. SAMPLE POPULATION: Strips of the circular and longitudinal muscle layers and taenia of the ventral colon from 14 horses. PROCEDURE: Muscle strips were suspended in tissue baths and attached to force transducers. Contractile activity of circular, longitudinal, and taenia muscle strips in response to electrical field stimulation was measured after addition of apamin and a nitric oxide inhibitor, N-nitro-L-arginine methyl ester (L-NAME). RESULTS: Electrical field stimulation reduced contractile activity in the circular muscle layer and taenia but not the longitudinal muscle layer. Addition of L-NAME significantly reduced inhibitory contractile activity at all frequencies for the circular muscle layer, whereas a significant effect was evident for the taenia only at the highest frequency. The combination of L-NAME and apamin resulted in a significant reduction in inhibition of the taenia at all frequencies but for circular muscle only at lower frequencies. CONCLUSIONS AND CLINICAL RELEVANCE: Nitric oxide and an apamin-sensitive neurotransmitter appear to mediate a component of inhibitory transmission in the circular muscle and taenia, but not the longitudinal muscle layer, of the equine ventral colon. Nitric oxide has a role in regulating contractile activity of the equine ventral colon, and nitric oxide synthase inhibitors may be useful in horses with ileus of the large colon.     

Effect of short-chain fatty acids on contraction of smooth muscle in the canine colon

OBJECTIVE: To determine effects of short-chain fatty acids (SCFA) on canine colonic smooth muscle. SAMPLE POPULATION: Colonic tissue obtained from 14 healthy dogs. PROCEDURE: Short-chain fatty acid (SCFA; acetate, propionate, and butyrate; 1 to 100 mmol/L)-induced contractions were compared with responses obtained with acetylmethylcholine (AMCh; 10(-4) mol/L). Roles of enteric neurons, cholinergic receptors, calcium stores in the sarcoplasmic reticulum, and extracellular calcium in the SCFA-induced responses were investigated by incubating muscle strips with tetrodotoxin (1 micromol/L), atropine (1 micromol/L), ryanodine (10 micromol/L), nifedipine (1 micromol/L), ethylene glycol-bis (beta-aminoethylether)-N,N,N',N'-tetra-acetate (EGTA; 0.1 mmol/L), or an extracellular calcium-depleted (zero extracellular calcium) solution prior to the addition of propionate or butyrate. RESULTS: Incubation with SCFA elicited isometric stress responses (0.25 to 2.15 x 10(4) N/m2) in colonic longitudinal smooth muscle. Maximal responses to butyrate and propionate (50 mmol/L) were 37 and 23%, respectively, of the maximal AMCh response. Acetate was least effective in stimulating contractile responses. Tetrodotoxin and atropine did not affect SCFA-induced contractions. Nifedipine and zero extracellular calcium solution abolished responses to butyrate and propionate, whereas EGTA attenuated (> 60%) but did not abolish those responses. Ryanodine did not affect SCFA-induced contractile responses. The SCFA did not affect colonic circular smooth muscle. CONCLUSIONS AND CLINICAL RESPONSE: The SCFA stimulate longitudinal but not circular colonic smooth muscle contractions via a direct effect on smooth muscle. The mechanism of the SCFA effect appears to involve the influx of extracellular calcium. These findings may account for some of the effects of fiber on canine colonic motility [corrected].     

Effects of prostaglandin F(2alpha) and nitric oxide on the secretory function of bovine luteal cells

The objective of the present study was to investigate the influence of prostaglandin F(2alpha) (PGF (2alpha)) and nitric oxide (NO) on production of steroids and PGs by culturing bovine luteal cells obtained from ovaries on days 8-12 of the estrous cycle with a nitric oxide (NO) donor (Spermine NONOate), and a NO synthase inhibitor (N(G)-nitro-L-arginine methyl ester dihydrochloride: L-NAME). When the cells were exposed for 24 h to PGF(2alpha) (10(-7)-10(-5) M), production of progesterone (P(4)) increased significantly at all doses used (P<0.05). Moreover, PGF(2alpha) stimulated PGF(2alpha) production (P<0.01), depressed testosterone (T) production (P<0.05), but did not affect synthesis of prostaglandin E(2) (PGE(2)). Spermine NONOate decreased P(4) production to 66%, 47% and 34% of the control concentration after treatment with 10(-5) M, 10(-4) M and 10(-3) M, respectively, but did not affect T production, and increased PGF(2alpha) synthesis (P<0.05) and PGE(2) (P<0.01) at all doses used. L-NAME increased production of P(4) (P<0.01) but did not affect (P>0.05) secretion of T, PGF(2alpha) and PGE(2). Estradiol-17beta (E(2)) was detectable on the level of sensitivity of assay and was not significantly altered by any treatments. The overall results suggest that PGF(2alpha) and NO produced locally in bovine CL play roles in the regulation of the secretory function of the bovine CL as auto/paracrine factors.     

Inhibition of spontaneous smooth muscle contractions in rat and rabbit intestine by blockers of the thromboxane A2 pathway

The effect of inhibitors of the thromboxane A2 pathway on spontaneous contractions of intestinal smooth muscle preparations was studied. The thromboxane A2 antagonists Bay u3405, SK and F 88046 and KW-3635 concentration-dependently inhibited both the amplitude and the frequency of spontaneous contractions of the longitudinal muscle from the rat proximal colon. A concentration-dependent inhibition of the myogenic contractions was also observed with the thromboxane A2 synthase inhibitor U-51605, and with the combined cyclooxygenase/lipoxygenase inhibitor nordihydroguaiaretic acid, whereas indomethacin, a pure cyclooxygenase inhibitor, was ineffective. None of these inhibitors affected the contractile response evoked by the cholinergic agonist carbachol, excluding non-specific actions on intestinal motility. A similar response was observed for the rabbit jejunum, which, in contrast to the rat colon, exhibits more regular, high-frequency spontaneous contractions, which were inhibited by Bay u3405, SK and F 88046 and KW-3635 in a concentration-dependent manner, whereas the response to carbachol remained unaffected. These results suggest a role for thromboxane A2 in the generation and/or facilitation of spontaneous smooth muscle contractions in the gut.     

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.     

Contractile effect of PGF2alpha and PGE2 on isolated branches of uterine and ovarian artery in different days of estrous cycle and early pregnancy in pigs

The contractile effects of PGF2alpha (3 x 10(-6) to 10(-4) M) and PGE2 (10(-7) to 10(-5) M) were examined on isolated branches of ovarian artery (OA) and extramyometrial branches of uterine artery (UA) collected from pigs in the luteal (day 10-12) and follicular phase (day 17-20) of the estrous cycle, and during early pregnancy (day 10-12). Strong contraction was demonstrated in both arteries during all investigated periods in response to PGF2alpha, which was significantly higher (P < 0.01) than to PGE2, being negligible in the follicular phase. In UA, the effective dose of PGF2alpha (ED50) amounted 7.9 x 10(-6) M and 6.3 x 10(-6) M in the luteal and follicular phase, and 5.0 x 10(-6) M in early pregnancy. ED50 for PGE2 reached 5.0 x 10(-7) M in the luteal phase, and 4.1 x 10(-7) M in early pregnancy. For both prostaglandins, the contraction was much stronger (P < 0.01) in OA than in UA branches. In OA, the ED50 for PGF2alpha was 1.2 x 10(-5) M in the luteal phase and was significantly higher (P < 0.05) than in the follicular phase (3.1 x 10(-6) M) and early pregnancy (2.7 x 10(-6) M). ED50 for PGE2 amounted 7.3 x 10(-7) M in the luteal phase and 1.7 x 10(-7) M in early pregnancy. Studies showed the influence of the estrous cycle and early pregnancy on OA branches sensitivity to the contractile effect of PGF2alpha and the lack of this effect on UA branches, and the influence of the estrous cycle on UA and OA branch contraction in response to PGE2.