Loperamide: evidence for a centrally mediated opioid effect on rumen motility in conscious goats and sheep

Loperamide inhibited the frequency and amplitude of cyclical contractions of the rumen in conscious goats (100 micrograms/kg, i.v. and sheep (250 micrograms/kg, i.v.). In goats, the inhibitory effect of loperamide could be prevented by pretreatment with the opiate antagonist naltrexone (greater than or equal to 12.5 micrograms/kg, i.v.) but not by pretreatment with the dopaminergic antagonist domperidone (500 micrograms/kg, i.v.). Intracerebroventricular administration of 1 microgram/kg loperamide in goats significantly depressed ruminal contraction frequency, whereas intravenous administration of 10 micrograms/kg loperamide did not affect cyclical motility. Administered via the carotid artery, loperamide (4 micrograms/kg) depressed both frequency and amplitude of cyclical contractions of reticulum and rumen, whereas the same dose was ineffective via the coeliac artery. In vitro, loperamide (10 nM-100 microM) had no influence on spontaneous activity or tone of the reticular longitudinal muscle strips. It is concluded that loperamide inhibits cyclical ruminal contractions through a central opioid pathway.     

Xylazine-induced mydriasis in rats and its antagonism by α-adrenergic blocking agents

Pupillary response to xylazine (10-300 micrograms/kg, i.v.) norepinephrine (1-30 micrograms/kg. i.v.) and atropine (3-100 micrograms/kg, i.v.) were observed in rats anaesthetized with pentobarbital. Xylazine caused a dose-dependent mydriasis which was antagonized by a selective alpha 2-adrenergic blocking agent, yohimbine (2.5 mg/kg, i.v.). was less effective in antagonizing this effect of xylazine. A selective alpha 1-adrenergic blocking agent, prazosin (2.5 mg/kg, i.v.) was ineffective in reducing the xylazine-induced mydriasis. In contrast, both phentolamine and prazosin blocked the pupillary dilation produced by norepinephrine, while yohimbine was much less effective in antagonizing norepinephrine-induced mydriasis. Atropine also induced a dose-dependent mydriasis which was not affected by yohimbine pretreatment. The present study suggests that the mydriatic effect of xylazine in the rat is mediated by an adrenergic mechanism, possibly by stimulating the alpha 2-adrenergic receptors in the iris and CNS.     

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.     

Effects of tolazoline and yohimbine on xylazine-induced central nervous system depression, bradycardia, and tachypnea in sheep

We compared the ability of tolazoline and yohimbine to antagonize xylazine-induced central nervous system depression, bradycardia, and tachypnea in 9 ewes and 5 rams. Once a week for 3 weeks, each sheep received one IV treatment of 0.4 mg xylazine/kg, 0.4 mg xylazine/kg followed in 10 minutes by 2 mg tolazoline/kg, or 0.4 mg xylazine/kg followed in 10 minutes by 0.2 mg yohimbine/kg. The order of the 3 treatments in each sheep was randomized. Xylazine alone caused recumbency for 41.0 +/- 3.7 minutes (mean +/- SEM). Tolazoline and yohimbine shortened the xylazine-induced recumbency to 12.1 +/- 0.9 minutes and 18.1 +/- 1.5 minutes, respectively. Sheep given xylazine alone had head droop for 34.0 +/- 5.4 minutes after rising. Head drooping of sheep given tolazoline or yohimbine was reduced to 10.1 +/- 1.7 minutes and 14.2 +/- 1.7 minutes, respectively. Both tolazoline and yohimbine reversed the bradycardia and tachypnea that followed xylazine administration. No statistical differences in the rate and magnitude of the reversal were observed between the 2 drugs.     

Antagonistic effects of alpha-adrenoceptor blocking agents on reticuloruminal hypomotility induced by xylazine in cattle.

The intravenous injection of a standard dose (0.05 mg/kg) of xylazine inhibited reticuloruminal motility in cattle. Pretreatment with adrenoceptor antagonists showing alpha 2-blocking activity, tolazoline (0.5 mg/kg) and yohimbine (0.2 mg/kg), antagonized the xylazine-induced reticuloruminal amotility. Tolazoline was more effective than yohimbine, since an antagonistic effect was not seen at 0.5 mg/kg yohimbine, and yohimbine at 0.2 mg/kg was less effective than tolazoline at 0.5 mg/kg. An adrenoceptor antagonist showing alpha 1-blocking activity, prazosin, did not prevent the inhibition of reticuloruminal motility by xylazine. The xylazine-induced reticuloruminal amotility was also not prevented by either a dopamine receptor antagonist, domperidone, or an opiate receptor antagonist, naloxone. These results suggest that xylazine inhibits bovine reticuloruminal motility through its activation of alpha 2-adrenoceptors, and show that tolazoline can be used as a specific antagonist of xylazine in studies of the alpha-adrenergic influence on reticuloruminal motility in cattle.     

Central and peripheral serotonergic control of forestomach motility in sheep

Participation of tryptaminergic receptors in the control of forestomach motility was investigated in conscious sheep using strain-gauges and chronically implanted electrodes. Two hours after feeding the sheep, serotonin (5-HT) was infused into the jugular vein (i.v.), or the carotid artery (i.c.), or into the lateral cerebral ventricles (i.c.v.), over a 10-min period. An i.v. dose of 16 micrograms/kg/min abolished the cyclic propagated contractions throughout the forestomach, increased ruminoreticular tone, and induced simultaneous contractions of all the parts of the rumen. A dose of 1.6 micrograms/kg/min i.c. or i.v. 5-HT inhibited phasic contractions. The effects of 5-HT were blocked completely by i.c.v. administration of methysergide (20 micrograms/kg) and imipramine (200 micrograms/kg), and blocked partially by naloxone (25 micrograms/kg), but unaffected by atropine (50 micrograms/kg). The inhibitory effects of i.v. 5-HT were antagonized by methysergide (200 micrograms/kg, i.v.) but unaffected by imipramine (2 mg/kg, i.v.) and atropine (250 micrograms/kg, i.v.). Only the i.v. administration of methysergide blocked the inhibition induced by i.c. infusion (1.6 micrograms/kg/min) of 5-HT. It is suggested that 5-HT exhibits an inhibitory control on forestomach phasic contractions through hypothalamic and bulbar 5-HT receptors, and exerts peripheral excitatory effects on the tone of the rumen wall.     

Influence of yohimbine and tolazoline on the cardiovascular, respiratory, and sedative effects of xylazine in the horse

To determine the effects of yohimbine and tolazoline on the cardiovascular, respiratory and sedative effects of xylazine, four horses were sedated with xylazine and treated with either yohimbine, tolazoline or saline. Xylazine was administered as an intravenous (i.v.) bolus (1.0 nig/kg) followed by a continuous infusion at the rate of 12 μg/kg/min. Heart rate, respiratory rate, mean arterial pressure, arterial blood gases, and the chin-to-floor distance were recorded throughout the experiment. After 60 min, either yohimbine or tolazoline was administered i.v. in incremental doses until reversal of sedation (defined as the return of the chin-to-floor distance to baseline values) was achieved. A control group in which a saline bolus was administered instead of an antagonist drug was included for comparison.
The average dose of yohimbine administered was 0.12 ± 0.02 (SEM) mg/kg. While the average dose of tolazoline was 7.5 ± 1.1 mg/kg. Both tolazoline and yohimbine antagonized the ventricular bradycardia and A-V conduction disturbances observed with xylazine administration. No change in mean arterial pressure was observed with xylazine or yohimbine administration, but tolazoline caused persistent mild systemic hypertension. There were no clinically significant changes in respiratory rate or arterial blood gas values with administration of either xylazine, yohimbine or tolazoline. The chin-to-floor distance decreased significantly with xylazine administration and increased significantly with administration of either yohimbine or tolazoline. In conclusion, both yohimbine and tolazoline successfully antagonized the cardiovascular and CNS depression associated with xylazine administration.     

Involvement of α-adrenoreceptors in the regulation of omasal cyclic myoelectrical activity in sheep

In five conscious adult ewes at rest, chronically implanted with electrodes in the musculature of the omasal wall, intravenous (i.v.) infusion for 30 min of alpha 1- or alpha 2-adrenergic receptor blockers, prazosin (20 micrograms/kg/min) and yohimbine (30 micrograms/kg/min), respectively, had no significant effects on omasal myoelectrical activity. The i.v. administration for 15 min of alpha 1- or alpha 2-agonists phenylephrine (4 micrograms/kg/min) or naphazoline (2.5 micrograms/kg/min), respectively, increased the frequency and the amplitude of groups of myoelectrical discharges of omasum, as well as the duration of its activity. Pretreatment of animals with prazosin blocked the responses to phenylephrine. Yohimbine prevented the effects of naphazoline dose-dependently. It is suggested that both alpha 1- and alpha 2-adrenoreceptors are involved in regulation of the sheep's omasal notility. This regulation did not seem to be a simple consequence of the changes in the reticular motility.     

Effects of idazoxan, tolazoline, and yohimbine on xylazine-induced respiratory changes and central nervous system depression in ewes

We compared the ability of 3 alpha 2-adrenoreceptor antagonists, idazoxan (0.05 mg/kg), tolazoline (2 mg/kg), and yohimbine (0.2 mg/kg) to reverse xylazine (0.3 mg/kg)-induced respiratory changes and CNS depression in 6 ewes. Once weekly, each ewe was given a random IV treatment of xylazine, followed in 5 minutes by either an antagonist or 0.9% NaCl solution. Xylazine alone caused recumbency for 54.2 +/- 5.3 minutes (mean +/- SEM). Xylazine also increased respiratory rate and decreased PaCO2 for at least 45 minutes, but did not significantly change arterial pH or PaCO2. Idazoxan and tolazoline were equally effective in reversing the respiratory actions of xylazine; however, yohimbine was less effective in reducing the respiratory rate and was ineffective in antagonizing the decreased PaO2. Idazoxan and tolazoline decreased the duration of xylazine-induced recumbency to 6.3 +/- 0.6 and 9.5 +/- 2.3 minutes, respectively, whereas yohimbine did not significantly change this effect of xylazine. Thus, at the dosages studied, idazoxan and tolazoline appeared to be more effective than yohimbine in reversing the respiratory and CNS depressant actions of xylazine in sheep.     

Effects of slaframine on ruminant digestive function: ruminal motility in sheep and cattle

Effect of purified slaframine (SF; 1-acetoxy-6-aminooctahydroindolizine), a parasympathomimetic secretagogue isolated from Rhizoctonia leguminicola, on ruminal motility was investigated in cattle and sheep. In trial 1, four ruminal cannulated wethers, fed a pelleted concentrate and hay diet, were injected intramuscularly with 0, 12, 24 and 48 micrograms SF/kg body weight (BW) in a 4 X 4 Latin-square design. Ruminal motility was recorded 1 h before and 1 to 2 h and 3 to 4 h after SF administration by measuring pressure changes exerted upon a fluid-filled, open-tipped catheter inserted into the dorsal sac of the rumen. The frequencies of both primary and secondary ruminal contractions were decreased as much as 20 to 78% with SF (P less than .05) depending upon the dosage level and time after administration. In trial 2, three ruminal-cannulated steers fed a concentrated diet were injected intramuscularly with 0, 12 and 24 micrograms SF/kg BW in a 3 X 3 Latin-square design. A water-filled balloon inserted into the cranial sac of the rumen was used to measure ruminal pressure changes 1 h before and 1 to 2 h, 3 to 4 h and 7 to 8 after SE administration. Frequency of primary and secondary ruminal contractions decreased with SF as much as 27 to 64% depending on the dosage level and time after administration. The frequency of secondary contractions increased 28% (P less than .05) as compared with control during the 7 to 8 h after administration.(ABSTRACT TRUNCATED AT 250 WORDS)     

Central and peripheral α-adrenoceptor actions of amitraz in the dog

The aim of this study was to determine the contribution of alpha 2- and alpha 1-adrenoceptor agonist activity of the formamidine, amitraz, on peripheral circulation in the dog. Intra-arterial injections of amitraz (0.25-5.0 micrograms/kg) produced a dose-dependent increase in perfusion pressure in the autoperfused hind limbs of methoxyflurane-anaesthetized dogs. A constant blood flow to the hind limbs was maintained using a peristaltic pump. Intravenous phentolamine (0.5 mg/kg), prazosin (35 micrograms/kg) and yohimbine (10 micrograms/kg) in separate experiments antagonized the vasoconstrictor actions of amitraz and produced a parallel shift to the right of the amitraz dose-response curve. Cumulative doses of amitraz (0.5-15 micrograms/kg) given by intracisterna magna (i.c.m.) injections reduced mean arterial pressure and heart rate in a dose-dependent manner. Similar responses were produced by intravenous amitraz but at much higher doses. In separate experiments amitraz-induced hypotension (doses up to 25 micrograms/kg i.c.m.) was prevented by pre-treatment with yohimbine (30 micrograms/kg i.c.m.) but not prazosin (20 micrograms/kg i.c.m.). Both antagonists partially inhibited the bradycardia produced by amitraz. It is concluded that amitraz stimulates alpha 1- and alpha 2-adrenoceptors to produce vascular constriction. The central hypotensive action of amitraz appears to be mediated by alpha 2-adrenoceptors; however, both receptor subtypes appear to be stimulated to produce bradycardia.     

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.     

The effects of jingsongling, a xylazine analog, on mean arterial blood pressure and heart rate in dogs — influences of yohimbine, tolazoline, prazosin, and atropine

The effects of jingsongling (JSL) and xylazine on heart rate (HR) and mean arterial pressure (MAP) were studied in five conscious male dogs. An i.v. injection of xylazine (1 mg/kg) caused a bradycardia, an initial hypertension, and a subsequent hypotension. An i.v. injection of JSL (1 mg/kg) caused a bradycardia and a 20-min hypertension without a subsequent hypotension. Atropine sulfate (45 micrograms/kg, i.v.) increased HR for 30 min without changing MAP, and antagonized JSL-induced bradycardia for at least 60 min. There was a subsequent rebound bradycardia. Atropine sulfate potentiated JSL-induced hypertension in both magnitude and duration. Yohimbine (0.1 mg/kg, i.v.), an alpha 2-adrenoceptor antagonist, increased HR and MAP for 110 and 70 min, respectively. Yohimbine not only failed to potentiate but even reversed the pressor effect of JSL in a dose-dependent manner. Yohimbine also caused a dose-dependent reversal of JSL-induced bradycardia. Tolazoline (5 mg/kg, i.v.), a nonselective alpha-adrenoceptor antagonist, increased MAP for 20 min without changing HR. Tolazoline also reversed JSL-induced hypertension and bradycardia. Prazosin (1 mg/kg), an alpha 1-adrenoceptor antagonist, decreased MAP and increased HR for at least 110 min. Prazosin reversed JSL-induced hypertension but failed to affect JSL-induced bradycardia. These results indicated that: (1) JSL-induced bradycardia and hypertension are mediated by alpha 2-adrenoceptors; (2) yohimbine and tolazoline may be useful in antagonizing these untoward reactions associated with JSL administration, whereas prazosin and atropine were not found to be beneficial in this regard.     

Alleviation of excessive gas accumulation in the ruminant stomach by ritanserin

The relationships between forestomach motility and eructation rate were studied in sheep and cattle. Three ewes and 2 heifers were implanted with strain gauges on the reticulo-rumen and fitted with a cannula in the dorsal sac of the rumen. Studies were performed in sheep after induction of hypocalcemia by Na2EDTA infusion and cattle were studied after ruminal distension. Experiments were performed by measuring the rate and volume of eructated ruminal gases, using a technique by which the trachea is transected. The frequency of reticulo-ruminal contractions decreased 40% within 30 minutes of Na2EDTA infusion to the sheep. The volume of eructated gas (for 30-minute periods) decreased from 10.7 L to 5.5 L at the end of the 60-minute infusion period. Pretreatment with ritanserin (0.1 mg/kg, subcutaneously) not only prevented bloating during the ruminal stasis induced by hypocalcemia, but also significantly increased the eructated volume of gas. In cattle, ritanserin given at the same dose level (0.1 mg/kg, subcutaneously) significantly increased the volume of eructated gas after ruminal distension. This study supports the hypothesis that the caudal esophageal sphincter has a role in the rate of ruminal gas eructation and indicates that its relaxation may be due to a 5-hydroxytryptamine antagonist.     

Modification by 6-hydroxydopamine (6-OHDA) of the inhibition of extrinsic rumen contractions in sheep produced by beta-endorphin

In sheep, beta-endorphin (1 and 2 micrograms/kg) administered into the third cerebral ventricle caused a significant inhibition of the frequency of rumen contractions. The amplitude of the first rumen contractions, following immediately after the end of infusion, and the average amplitude of primary rumen contractions, were inhibited. Beta-endorphin caused general psychomotor excitability. These results suggest that an inhibitory mu and delta opioid system is involved in the control of forestomach motility and general behaviour in sheep. All effects of beta-endorphin were completely prevented by i.c.v. 6-hydroxydopamine (6-OHDA, 18.2 micrograms/kg) pre-treatment. These results suggest that beta-endorphin-induced inhibition of rumen motility is due to central noradrenergic system activation. The exact location of this noradrenergic system remains to be determined.     

The cardiorespiratory effects of intrathecal xylazine in the conscious rabbit

The alpha 2 agonist xylazine produced a dose-dependent decrease in mean arterial blood pressure in conscious rabbits when injected intrathecally (i.t.) through a cannula previously implanted under general anaesthesia. Intrathecal administration of 200 and 400 micrograms of xylazine produced a significant reduction in arterial blood pressure from control values (maximum depressions of 25% and 33%, respectively). There was little effect on cardiac output and arterial carbon-dioxide tension and no effect on respiratory rate, arterial oxygen tension and pulse rate. Intrathecal injection of 100 microliters of 0.9% saline had no effect. Intravenous (i.v.) tolazoline (0.5 mg/kg) abolished xylazine-induced hypotension (200 micrograms) in four rabbits. Contrast radiography revealed that 100 microliters of solution injected i.t. in anaesthetized rabbits spread distally over eight vertebral spaces. There was little rostral spread. It was concluded that xylazine-induced hypotension following i.t. injection was due to local activation of alpha 2 adrenoceptors present in the thoracic spinal cord. It is postulated that spinal alpha 2 adrenoceptors may play an important role in the hypotension recorded in animals after parenteral injection of xylazine.     

Antinociceptive actions of intravenous a2-adrenoceptor agonists in sheep

The antinociceptive activity of the intravenously administered alpha 2-adrenoceptor agonists, clonidine and xylazine, was measured in sheep using thermal and mechanical pressure threshold detection systems. Both drugs demonstrated clear antinociceptive activity for both forms of threshold stimuli and clonidine at 6 micrograms/kg i.v. was more potent and longer lasting than xylazine at 50 micrograms/kg i.v. The antinociceptive effects were reversed by idazoxan (0.1 mg/kg i.v.), but were not affected by naloxone at 0.2 mg/kg i.v. indicating that these effects were mediated by alpha 2-adrenoceptors.     

Types of serotonergic receptors involved in the control of reticulo-ruminal myoelectric activity in sheep

The effects of peripheral (intravenous, i.v.) and central (intracerebroventricular, ICV) administrations of agonists of 5-HT_1A, 5-HT₂, 5-HT₃ and 5-HT₄ receptors were investigated in conscious sheep chronically fitted with intraparietal electrodes on the reticulum and the dorsal, ventral and caudo-ventral rumen. The 5-HT_1A agonist 8-hydroxydipropylaminotetralin increased reticular and decreased ruminal spike burst frequency when given i.v. (80 μg/kg) and ICV (8 μg/kg). The 5-HT₂ and 5-HT₃ agonists, α-methylserotonin and 2-methylserotonin, induced a moderate inhibition of rumino-reticular contractions when given i.v. at 100 and 150 μg/kg, respectively, while marked inhibition was observed after ICV administration at doses of 10 and 5 μg/kg, respectively. The 5-HT₄ agonist 5-methoxytryptamine strongly stimulated rumino-reticular motility by the ICV (10 μg/kg) route, whereas it induced a moderate inhibition when administered i.v. (200 μg/kg). The selective antagonist of 5-HT_1A, 5-HT₂, 5-HT₃ and 5-HT₄ receptors, spiroxatrine, ritanserin, granisetron and DAU 6285, respectively, blocked the responses of the respective agonists given by the same route. Moreover, the antagonists given ICV blocked the effects of the agonists given i.v. except for DAU 6285 ICV, which did not antagonize the inhibition induced by 5-methoxytryptamine i.v. It is concluded that the four types of serotonergic receptors investigated control rumino-reticular motility at the central level. However, according to the receptor type and the forestomach area (reticulum or rumen) this control may be stimulatory or inhibitory, demonstrating a pleiotropic role of serotonin in the control of rumino-reticular motility in sheep.     

Selectivity of atipamezole, yohimbine and tolazoline for alpha-2 adrenergic receptor subtypes: Implications for clinical reversal of alpha-2 adrenergic receptor mediated sedation in sheep

The α₂-adrenergic receptor antagonists, yohimbine, atipamezole and tolazoline, are used in veterinary medicine as reversal agents for the sedative/hypnotic effects of α₂-agonists. Ruminants have increased sensitivity to the sedative/hypnotic effects of α₂-agonists compared to other species. The receptors mediating the sedative effects of α₂-agonsts are located primarily on locus coeruleus neurons in the pons of the lower brainstem. Four pharmacological subtypes of the α₂-adrenergic receptor (A,B, C and D) have been identified based on differences in ligand affinity. The aim of this study was to: 1) determine the pharmacological profile of atipamezole, yohimbine and tolazoline at the four α₂-adrenergic receptor subtypes and; 2) determine whether these agents differ in their affinities at the α₂-adrenergic receptor present in the sheep brainstem. In inhibition binding studies against the selective α₂-adrenergic receptor ligand [³H]-MK-912, tolazoline showed the lowest affinity for all four α₂-adrenergic receptor subtypes compared to yohimbine and atipamezole. The affinities of yohimbine and atipamezole were similar at the α_2A-, α_2B- and α_2C-adrenergic receptors but differed by approximately 100 fold at the α_2D-adrenergic receptor. Atipamezole had a 100 fold higher affinity at the α_2D-adrenergic receptor when compared to yohimbine. To determine the ligand binding characteristics of these agents at the α₂-adrenergic receptor in sheep brainstem, membranes were labelled with [³H]-MK-912 and inhibition competition curves were performed. Atipamezole showed approximately a 100 fold higher affinity for the sheep brainstem α₂-adrenergic receptor compared to yohimbine which was similar to what was observed for the α_2D-adrenergic receptor in PC12 cells transfected with RG-20. The results from these studies suggest that atipamezole has a high affinity for the α_2D-adrenergic receptor that appears to be the receptor subtype in sheep brainstem.     

Central and peripheral β-adrenergic influences on reticulo-rumen and upper-gut myoelectrical activity in sheep

The effects of intravenous (i.v.) and intracerebroventricular (i.c.v.) administration of beta-adrenoceptor agonists were evaluated on the reticulo-rumen and upper-gut myoelectrical activity in six ewes chronically fitted with intraparietal electrodes and a cannula in a lateral ventricle of the brain. Intravenous infusion of the beta 1 agonist dobutamine (30 micrograms/kg/min for 15 min) reduced the frequency of reticulo-ruminal and abomasal contractions and stimulated duodeno-jejunal motility, inducing a Phase III on the jejunum. These effects were reproduced by i.c.v. dobutamine at a dose of 10 micrograms/kg. Intravenous infusion of the beta 2 agonist ritodrine (15 micrograms/kg/min for 15 min) selectively inhibited antral and duodenal motility. Ritodrine i.c.v. (15 micrograms/kg) did not affect forestomach or gastrointestinal motility. The mixed beta 1, beta 2 agonist isoprenaline infused i.v. (0.6 micrograms/kg/min for 15 min) reproduced the effects of i.v. dobutamine, except at the antro-duodenal level which was strongly inhibited. The effects of i.v. dobutamine were antagonized by i.v. or i.c.v. acebutolol, a specific beta 1 antagonist. The effects of i.v. ritodrine were blocked by i.v. but not i.c.v. administration of propranolol, a mixed beta 1, beta 2 antagonist. These data indicate that the stimulation of central beta 1 adrenoceptors inhibits forestomach and antral motility and stimulates duodeno-jejunal motility. Stimulation of peripheral beta 2 adrenoceptors selectively inhibits duodeno-jejunal motility.