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.     

Influence of dopamine on rumino-reticular motility and rumination in sheep

The effects of intracerebroventricular (i.c.v.) and intravenous (i.v.) administration of dopamine and its antagonists (domperidone and metoclopramide) on forestomach motility were investigated in four sheep fitted with Nichrome electrodes and strain gauges implanted on the reticulum and the caudo-dorsal sac of the rumen. Infused by the i.c.v. route at a rate of 2 micrograms . kg-1 . min-1, dopamine inhibited the phasic contractions of the reticulo-rumen. A similar effect was obtained following i.v. administration of doses which were 10 times higher, but the effect was associated with an increased tone of the rumen wall. Prior i.v. administration of domperidone (0.5 micrograms . kg-1) blocked these effects and a selective blockade of the dopamine-induced inhibition of phasic contractions was obtained with higher dose of domperidone (2.5 micrograms . kg-1) administered centrally. When dopamine was infused alone ventricularly or intravenously after metoclopramide (40 micrograms . kg-1), it induced a transient (6-8 min) period of rumination, which could be blocked by a prior i.c.v. administration of tolazoline. It was concluded that dopamine acts on rumino-reticular motility in sheep through specific dopamine receptors (i) centrally by inhibiting the frequency of reticular contraction and (ii) peripherally by increasing the muscular tone of the rumen, and its effects on rumination involved alpha 2 adrenergic receptors located in the central nervous system.     

Modification by domperidone of dopamine- and apomorphine - induced inhibition of extrinsic ruminal contractions in goats

Goat ruminal strips reacted with an increase in smooth muscle tone after exposure to apomorphine. This rise in tone could be blocked by domperidone, but not by naltrexone. In vivo , both dopamine and apomorphine caused inhibition of extrinsic ruminal contractions. These effects were completely prevented by domperidone pretreatment, whereas naltrexone was not an effective antagonist. These results suggest that apomorphine-induced inhibition of rumen motility is due to DA-receptor activation. The exact location of these DA-receptors remains to be determined.     

Pharmacological evaluation of sheep lung strip

Isolated sheep lung parenchymal strips responded to histamine > carbachol > PGF_2a > 5-HT with contractions, and to isoproterenol (Isop), and to large doses of epinephrine (E), norepinephrine (NE) and phenylephrine (PE) with relaxations. PGF_2a-contracted lung strip responded to PGE₁ and PGE₂ with relaxation. The strips which were partially contracted to histamine, PGF_2a, 5-HT and carbachol also responded to isop, E and NE with relaxations. Histamine responses were not modified by metiamide (an H₂-receptor antagonist). Mepyramine and atropine selectively antagonized contractions to histamine and carbachol, respectively. After β-blockade with propranolol, lung strips responded to NE > E > PE > isop with contractions, which were inhibited or reversed by phentolamine and dibenzyline. It is concluded that H₁ receptors are present in sheep peripheral airway smooth muscles, and that a- and β-adrenoceptors mediate contraction and relaxation, respectively, in sheep lung strips.     

α-Adrenergic control of gonadotropin secretion in the ewe

The effect of the centrally acting α-adrenoceptor agonist, clonidine, on plasma LH and FSH was studied in oestradiol-primed and unprimed ewes and in oestrous ewes. In unprimed anoestrous ewes, clonidine stimulated LH and FSH release after a lag period of 18 h, and noradrenaline intracarotid injection or i.v. infusions immediately stimulated LH release. In oestradiol-infused anoestrous ewes, clonidine produced either a delay or inhibition of the gonadotrophin surge and noradrenaline i.v. infusion advanced the LH surge. In oestrous ewes treated with clonidine, there was marked delay in the LH surge, but the magnitude of the LH and FSH surges were unaffected. Intravenous administration of α-adrenoceptor blockers, phentolamine and phenoxybenzamine, blocked the oestradiol-induced gondotrophin surge in anoestrous ewes. The effect of phenoxybenzamine on gonadotrophin surge was dose dependent in oestrous ewes. Small doses (4 mg/kg i.v.) of phenoxybenzamine delayed the synchronous LH and FSH surges. There was complete blockade of the LH surge and partial blockade of FSH surges in ewes given phenoxybenzamine (8 mg/kg i.v.) before the expected synchronous gonadotrophin surges. After this experiment, the initial rise of plasma progesterone concentrations did not occur until day 6 of oestrous cycle. Administration of phenoxybenzamine before the expected second FSH surge had no effect on the second FSH surge. Gonadotrophin release induced by gonadotrophin-releasing hormone was attenuated by phenoxybenzamine, but not by clonidine. The results suggest that the LH surge is under α-adrenergic control and the first FSH surge is under partial α-adrenergic control, but the second FSH surge is not under α-adrenergic control. The results also suggest oestradiol modulation of α-adrenergic receptor action.     

Depression of reticulo-ruminal motor functions through the stimulation of 012-adrenoceptors

Inhibition of the cyclical contractions of the reticulum and the rumen by detomidine (10-40 micrograms/kg, i.v.), xylazine (20-80 micrograms/kg, i.v.) and clonidine (2.5-10 micrograms/kg, i.v.) were compared in sheep and cattle housed individually in box stalls. Two alpha 2-adrenergic receptor blocking agents, tolazoline and yohimbine, were administered intravenously for prevention (0.1-0.4 mg/kg) or reversal (0.4-1.2 mg/kg) of these effects. Continuous recording of the reticuloruminal contractions and measurement of the volume of ruminal gas eliminated through the upper respiratory tract indicated that the three alpha 2-agonists inhibited the primary ruminal contractions associated with the reticular contractions. The occurrence of secondary ruminal contractions was also blocked in sheep, but only suppressed in cattle. The inhibition of reticulo-ruminal contractions was prevented or reversed competitively by the two alpha 2-blocking agents, suggesting an alpha 2-adrenoceptor mediation of the inhibition of cyclical motor activity of the reticulo-rumen. In contrast with tolazoline, yohimbine was unable to alleviate the accumulation of gas resulting from inhibition of the secondary ruminal contractions.     

Effects of chlorpromazine on plasma concentrations of long chain fatty acids and glucose in sheep

Intravenous chlorpromazine was found to cause rapid increases in plasma concentrations of glucose and long chain fatty acids in adult sheep of both sexes. α-adrenergic blockade with phentolamine suppressed the increase in glucose concentration but not the increase in concentration of long chain fatty acids caused by chlorpromazine. β-adrenergic blockade with propranolol suppressed the increase in concentration of long chain fatty acids but not the increase in glucose concentration caused by chlorpromazine. These results were consistent with the hypothesis that chlorpromazine caused a systemic release of epinephrine.     

Gastro-intestinal motor disturbances induced by lysine-acetylsalicylate treatment in sheep

The effects of intravenous (i.v.), intramuscular (i.m.) and oral administration of lysine-acetylsalicylate (Lys-ASA) on gastro-intestinal motility were investigated in sheep using electromyography. A dose of 20 mg/kg Lys-ASA intravenously reduced the frequency of reticular contractions for 86 ± 18 min, produced abomasal hypomotility and caused a disruption of the cyclical pattern of intestinal motility for at least 120 min. The frequency of reticular contractions measured from 20 to 30 min after Lys-ASA administration was negatively correlated (ß= 0.97; PΔ0.01) to the log of the dose used for doses varying from 10 to 40 mg/kg. Similar effects were observed with intramuscular and oral dose rates of 40 and 80 mg/kg, respectively. Previous i.v. administration of phentolamine (0.1 mg/kg) or tolazoline (2 mg/kg) abolished the effects of Lys-ASA (20 mg/kg) administered intravenously on both reticular contractions and abomaso-intestinal motility.
It was concluded that Lys-ASA administered at therapeutic doses in sheep produced gastro-intestinal motor disturbances and that α-and α₂-adrenergic antagonists are able to block them.     

Autonomic and autacoid activity in antigen-sensitized and control ovine pulmonary vein and artery

Spirally cut strips of ovine pulmonary vein and artery were studied in isolated organ baths and their responses to selected autacoid and autonomic agents were compared. In addition blood vessels taken from horse plasma-sensitized sheep were compared with their respective controls. Pulmonary vein and artery exhibited qualitative and quantitative differences in their autacoid and autonomic reactivity. Veins were more sensitive in responding with contractions to histamine (HIST) and carbachol (CARB) when compared with arteries. Responses of these vessels differed qualitatively to 5-Hydroxytryptamine (5HT); phenylephrine (PE) and adrenaline (ADR): arteries responded with strong contraction and veins with relaxations. Isoproterenol (ISOP) effectively relaxed veins but was either without effect or produced 10%–15% relaxations of precontracted arterial strips. Phentolamine competitively antagonized ADR and PE-induced contractile responses of arteries while on veins, ISOP and PE dose—response curves (DRCs) were shifted to the right in the presence of propranolol. Mepyramine inhibited venous and arterial responses to HIST.
Comparisons between sensitized and non-sensitized sheep vasculature revealed a significant ( P < 0.05) decrease in the activity of spasmolytic agonists on veins, i.e. relaxant actions of 5HT, PE and ISOP were significantly impaired. In addition the activity of 5HT to contract pulmonary artery was significantly ( P < 0.05) increased when compared with controls. Present investigation suggests: (i) the predominance of H₁-histaminergic receptors in ovine pulmonary vasculature; (ii) the preponderance of α and β-adrenergic receptors in pulmonary artery and vein, respectively; (iii) that antigenic sensitization exaggerates the pathological state by causing a decrease in spasmolytic activity with a parallel increase in spasmogenic activity.     

Vasomotor effects of histamine on bovine and equine basilar arteriesin vitro

The vasomotor effects of histamine on isolated bovine and equine basilar arteries were examined. Histamine induced contractions in both these preparations. The maximal response to and pEC₅₀ value for histamine of the equine artery were larger than those of bovine tissue. Similar results were obtained with endothelium-denuded basilar arteries. Diphenhydramine (H₁-receptor antagonist) inhibited histamine-induced contractions of the basilar arteries from both species in a concentration-dependent manner and its pA ₂ values (with 95% confidence limits) were 7.61 (7.39–7.83) and 8.15 (8.01–8.29) for the bovine and equine preparations, respectively. Cimetidine (H₂-receptor antagonist) slightly potentiated histamine-induced contractions of bovine, but not equine, basilar arteries. 2-Thiazolylethylamine (H₁-receptor agonist) induced contractions in both preparations, whereas impromidine (H₂-receptor agonist) induced weak relaxation of the bovine, but not the equine, tissue. These findings indicate that bovine basilar arterial smooth muscle cells possess H₁- and H₂-receptors. Stimulation of the former results in contraction, whereas stimulation of the latter results in weak relaxation. Equine basilar arterial smooth muscle cells possess H₁-receptors, stimulation of which results in contraction.Abbreviations CR concentration ratio - EC₅₀ concentration producing 50% maximal response - pA ₂ negative logarithm of the molar concentration of antagonist that produces a twofold rightward shift of a concentration-response curve - pEC₅₀ negative logarithm of EC₅₀ - PGF₂ prostaglandin F₂ - PGI₂ prostaglandin I₂     

Histamine relaxes constricted trachea and bronchi of horse

Horse trachea and bronchi contracted to slow-reacting substance of anaphylaxis, carbachol, 5-hydroxytryptamine, histamine, 2-methyl-histamine, bradykinin and prostaglandin F₂. Prostaglandins E₁ and E₂, isoprenaline and 4-methylhistamine caused relaxation of carbachol-contracted bronchi. Mepyramine (H₁-blocker) specifically inhibited histamine bronchoconstriction. In the presence of mepyramine, histamine caused relaxation of carbachol-contracted bronchi. Metiamide (H₂-blocker) inhibited histamine bronchorelaxation but not relaxation of the trachea. This suggests (1) the presence of both H₁- and H₂-receptors mediating bronchoconstriction and relaxation respectively (2) the existence of an atypical histamine receptor in the trachea. The study suggests that in equine respiratory hypersensitivity under therapy with classical (H₁) antihistaminics, further release of histamine may exert a beneficial broncholytic effect on airways contracted by other chemical mediators of immediate-type inflammation.     

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.     

Characterization of muscarinic receptor subtype mediating contraction and relaxation in equine coronary artery in vitro

In coronary arterial rings isolated from horses, 10-^-8-10^-6 mol/l acetylcholine (ACh) induced concentration-dependent contractions which were potentiated by the removal of endothelium and by pretreatment with I,-nitro-arginine (LNAG) or methylene blue (MB). Relatively lower concentrations of Ach 10-¹⁴-10-⁸ mol/l) induced relaxation when the coronary rings were contracted by phenylephrine (PE). ACh-induced contractions in the coronary rings without endothelium were competitively inhibited by each muscarinic subtype selective antagonist in the following order of potency: 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP) > pirenzepine ≥ parafluoro-hexahydrosiladiphenidol (pFHHSiD) > methoctramine. ACh-induced relaxation in the rings with endothelium was inhibited by LNAG or MB, and by each selective antagonist in the following order of potency: 4-DAMP < pFHHSiD ≥ pirenzepine ≥ methoctramine. These results suggest that the ACh-induced contraction and relaxation in equine coronary arteries are mediated mainly by an M₃-receptor located on the smooth muscle cells and endothelial cells, respectively, and that the stimulation of the M₃-receptor on the endothelial cells liberates nitric oxide.     

Preliminary pharmacological characterization of ovine mesenteric vasculature

Spirally cut strips of ovine mesenteric vein and artery were studied in isolated organ baths. No qualitative differences were observed in the autonomic and autacoid reactivity of these blood vessels. Both arterial and venous preparations responded in a dose-related manner to 5HT greater than or equal to adrenaline greater than phenylephrine greater than histamine. The responses of venous and arterial strips to 5HT were antagonized by methysergide while mepyramine inhibited histamine-induced contractions. Phentolamine competitively inhibited adrenaline on arteries. Vascular preparations, incubated with mepyramine (2 X 10(-7) M) and contracted half-maximally with 5HT, responded with relaxations to the higher doses of histamine. Specific H2-agonists, impromidine and dimaprit also caused relaxations of half-maximally contracted venous and arterial strips. Impromidine was approximately 500-5000 times more potent than histamine and dimaprit. Trimetaquinol effectively relaxed both venous and arterial preparations while isoproterenol had either no effect or produced weak contractions/relaxations. This investigation suggested the presence of (i) both excitatory and inhibitory receptors for histamine, (ii) D-tryptaminergic receptors mediating contractile effects of 5HT, and (iii) a predominance of alpha-adrenergic receptors, in the mesenteric vasculature of sheep.     

Effects of metoclopramide, clenbuterol and butorphanol on ruminoreticular motility of calves

Rate and amplitude of contractions of the rumen dorsal sac and reticulum of 6 male Holstein calves ages 12 to 20 weeks were monitored with electromyography, strain gauges and an intraruminal pressure catheter. Heart rate and mean arterial pressure were measured with ultrasound. The effects of metoclopramide, a dopamine antagonist, clenbuterol, a beta-2 adrenergic agonist, and butorphanol, a narcotic agonist/antagonist, were observed utilizing dosages bracketing those employed clinically. Metoclopramide significantly decreased the intraruminal pressure peaks associated with cyclical contractions without changing their rate. Clenbuterol had no measurable effect on the ruminoreticulum. Butorphanol totally inhibited ruminoreticular contractions for periods of 6 to greater than 40 min depending on dosage. Only clenbuterol significantly affected cardiovascular function; it increased heart rate and decreased mean arterial pressure. Both metoclopramide and butorphanol produced behavioral changes in the calves.     

Food intake and rumen motility in dwarf goats. Effects of atipamezole on the inhibitory effects induced by detomidine,medetomidine and romifidine

The effects of some ₂-adrenoceptor agonists and of the ₂-adrenoceptor antagonist atipamezole on food intake and ruminal contractions were studied in dwarf goats. Detomidine, 0.2 µg/kg per min for 10 min, failed to modify food intake during either the first or second observation period (0–30 min and 180–210 min after drug infusion, respectively). Given at a higher dose rate (0.4 µg/kg per min for 10 min), the drug inhibited food consumption during the first observation period, but stimulated food intake during the second period. A similar pattern was observed after IV infusion with medetomidine (0.2 µg/kg per min for 10 min), romifidine (0.4 µg/kg per min for 10 min) or xylazine (1 µg/kg per min for 10 min). The ₂-antagonist atipamezole (2 µg/kg per min for 10 min) failed to modify food intake during either the first or second observation period. After treatment with atipamezole, the effects of ₂-agonists on feeding behaviour were completely antagonized.The ₂-agonists administered at similar dose rates to those used in the food intake experiments induced bradycardia, decreases in body temperature and inhibition of ruminal contractions. The inhibition of ruminal contractions induced by romifidine was partly antagonized by atipamezole pre-treatment. These findings demonstrate that the ₂-agonist-induced changes in ruminal contractions do not simply cause changes in feeding behaviour. The drop in body temperature induced by ₂-agonists was prevented by atipamezole pre-treatment, whereas the induced bradycardia was not modified by this ₂-antagonist.Abbreviations IV intravenous - SEM standard error of the mean     

Dopamine-sensitive receptors that evoke rumination and modify reticulo-ruminal activity in sheep

Dopamine (20 micrograms/kg) evoked rumination in sheep when injected as a bolus into the coeliac artery or into the left gastric artery but not when injected into the carotid artery. A mixed alpha-adrenoreceptor antagonist (phentolamine) and an alpha 2-adrenoreceptor antagonist (yohimbine) prevented dopamine from evoking rumination, but a dopaminergic antagonist (metoclopramide) did not. These findings suggest that dopamine stimulated rumination by acting upon alpha 2-adrenoreceptors situated in the area supplied by the left gastric artery, whereas dopamine injected intracerebrally may have evoked rumination by an alpha 2-adrenoreceptor effect in the central nervous system (Bueno et al., 1983) and the actions of intrajugular dopamine were exclusively upon peripheral adrenoreceptors located specifically in the gastric area. Dopamine (1 microgram/kg/min) infused into the carotid artery reduced the frequency of reticular contractions by acting upon a centrally located dopaminergic receptor mechanism sensitive to metoclopramide but not to phentolamine. When dopamine was infused into the coeliac artery or into the left gastric artery, the amplitude of reticular contractions was reduced by a peripheral mechanism sensitive both to metoclopramide and to phentolamine. Dopamine also reduced the amplitude of reticular contractions when infused into the carotid artery but to a lesser degree than when given into the coeliac or left gastric artery.     

Effects of papaverine on carbachol- and high K+-induced contraction in the bovine abomasum

The effects of papaverine on carbachol (CCh) -and high K⁺- induced contraction in the bovine abomasum were investigated. Papaverine inhibited CCh (1 µM) -and KCl (65 mM) -induced contractions in a concentration-dependent manner. Forskolin or sodium nitroprusside inhibited CCh-induced contractions in a concentration-dependent manner in association with increases in the cAMP or cGMP contents, whereas papaverine increased cGMP contents only at 30 µM. Changes in the extracellular Ca²⁺ from 1.5 mM to 7.5 mM reduced verapamil-induced relaxation in high K⁺-depolarized muscles, but papaverine-induced relaxation did not change. Futhermore, papaverine (30 µM) and NaCN (300 µM) decreased the creatine phosphate contents. These results suggest that the relaxing effects of papaverine on the bovine abomasum are mainly due to the inhibition of aerobic energy metabolism.     

Role of Eicosanoids in the Regulation of the Periparturient Period in Cattle

Contents: In this review, the role of eicosanoids in regulation of parturition and the postpartum period was described with special emphasis on the bovine species. The metabolism of arachidonic acid and the production of eicosanoids during the peripartum period was discussed. Prostaglandin E₂ and F_2α (PGE₂, PGF_2α) play an important role in mechanisms controlling parturition. They are involved in luteolysis, uterine contractions and dilation of the cervix. Eicosanoids also seem to influence the loosening processes of the fetal membranes. However, in the literature, conflicting results were found. Many investigations suggested that retained placental membranes could be related to low PGF_2α production and/ or an imbalance of arachidonic acid metabolism in the uterus. The possible role of the lipoxygenase pathway metabolite 15-hydroxy-eicosatetraenoic acid (15-HETE) in expulsion of the fetal membranes was also discussed. As far as the postpartum period is concerned, a relationship between postpartum PGF_2α release and the involution of the uterus was found. Cows with undisturbed uterine involution had higher PGF_2α production than cows with delayed involution. In contrast to the positive effect of PGF_2α on uterine involution, PGE₂ seems to delay the involution processes. Further experiments are necessary in order to study the function of eicosanoids in mechanisms regulating parturition, release of the fetal placental membranes and involution of the uterus.     

Effects of dopamine receptor agonists on food intake and rumen motility in dwarf goats

Kaya, F., Van Duin, C.T.M. & Van Miert, A.S.J.P.A.M. Food intake and rumen motility in dwarf goats. Effects of some dopamine receptor agonists. J. vet. PharmacolTherap, 17 , 120–126. In ruminants, the dopaminergic regulation of feeding behaviour has not been investigated. Therefore, the effects of dopamine receptor agonists and antagonists on food intake and forestomach motility were studied in dwarf goats Goats treated i.v. with bromocriptine (1 μg or 2.5 μg/kg body wt/min during 10 min) ate less food than when treated with saline. This inhibitory effect on food intake could not be prevented by the peripheral dopamine receptor antagonist domperidone (0.5 mg/kg body wt i.v.). In contrast, dopamine (i.v. 20 μg/kg body wt/min during 15 min), levodopa (i.v. 40 μg/kg body weight during 10 min), apomorphine (i.v. 2 μg/kg body wt/min during 10 min) and lisuride (i.v. 0.2 μg/kg body wt/min during 15 min and 0.5 μg/kg body wt during 10 min) failed to modify food intake. Given in association with benserazide, a decarboxylase inhibitor (i.v. 20 μg/kg body wt/min during 10 min), levodopa was still inactive as an anorectie agent. Levopoda, bromocriptine and lisuride administered at similar dose rates to those which were used in the food intake experiments, induced some clinical signs including inhibition of forestomach contractions. The inhibition of rumen contractions induced by these drugs was completely antagonized by domperidone pretreatment. These results, together with earlier in vivo and in vitro observations, suggest that the inhibitory effects of dopamine receptor agonists on forestomach contractions are due to interactions with peripheral dopaminergic receptors. The change in smooth muscle tension, which leads to a change in the signals transmitted via vagal afferents to the central nervous system, probably does not modify feeding behaviour in dwarf goats. Furthermore, i.v. infusion of lisuride induced rumination when the inhibition of the forestomach contractions was prevented by domperidone; this effect may involve α₂-adrenoceptor activation.