5‐Hydroxytryptamine induces forestomach hypomotility in sheep through 5‐HT4 receptors

Abstract

SUMMARYThe effects evoked by 5-hydroxytryptamine (5-HT; serotonin) on forestomach myoelectric activity were investigated in conscious sheep. Myoelectric signals were recorded with electrodes chronically implanted in the reticulum, rumen (dorsal sac) and omasal body, and were analysed by a computer-based method. The 5-HT receptors and the neuronal pathways involved in these actions were studied. The intravenous (i.v.) infusion of 5-HT (8 ,ug kg-' min-' for 5 min) evoked an inhibition of activity of the whole forestomach. Methiothepin, injected i.v. at 0.1 mg kg-l, inhibited rumen secondary contractions and omasum activity. However, forestomach activity remained unchanged after the administration of 0 2 mg kg-of ketanserin, ondansetron, tropisetron, GR-1 13808, phentolamine, propranolol, domperidone and naloxone. Atropine (0.2 mg kg-), hexamethonium (2 mg kg-') or haloperidol (0.1 mg kg-') abolished rumen secondary cycles and inhibited omasum activity. In addition, atropine also suppressed primary cycles. GR-113808 blocked all 5-HT-induced effects. Furthermore, atropine or hexamethonium prevented the 5-HTevoked inhibition of reticulorumen primary cycles. In contrast, the remaining antagonists did not alter the 5-HT-evoked forestomach hypomotility. In conclusion, 5-HT induces inhibition of forestomach myoelectric activity through 5-HT4 receptors, these actions being mediated by cholinergic neural pathways involving muscarinic and nicotinic receptors. However, adrenergic, doparminergic or opiate pathways are not implicated.

Quantitative mRNA Analysis of Eight Bovine 5‐HT Receptor Subtypes in Brain, Abomasum, and Intestine by Real‐Time RT‐PCR

“…In another study in sheep, 5-HTR 1A , 5-HTR 2 , 5-HTR 3 , and 5-HTR 4 are reported to be involved in the regulation of forestomach motility occasionally recorded concomitantly to duodenal phase III activity (21,32). Furthermore, 5-HT is also implicated in the regulation of MMC patterns in the abomasum and proximal small intestine (17,(19)(20)(21)27,33), but little is known about the role of the respective 5-HTR subtypes involved in motility control in ruminants.…”

“…In ruminants, 5-HT has been shown to be involved in the regulation of forestomach, abomasal, and intestinal motility (21,(26)(27)(28)(29)(30). Most of the research available on the effects of 5-HT on GI motility in ruminants has been conducted in sheep.…”

“…We were especially interested in 5-HTR 1 , 5-HTR 2 , and 5-HTR 4 receptor subtypes, as these are expected to play most likely an important role in GI motility (4,17,21).…”

“…However, the serotoninergic pathways were predominantly studied in humans and rodents. The 5-HT was shown to be involved in the initiation and regulation of the myoelectric migrating complex (MMC), in the peristaltic reflex, in the regulation of stomach, small intestine and colon motility, as well as in intestinal secretion (4,9,(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23). The mechanisms of action of 5-HT in the digestive tract are not completely understood and the role of 5-HTR subtypes in the regulation of GI motility differs among species and locations along the GI tract (9,24,25).…”

Evidence for the involvement of 5‐HT4 receptors in the 5‐hydroxytryptamine‐induced pattern of migrating myoelectric complex in sheep

“…In man, 5‐HT inhibits spontaneous motility in circular muscle strips of the colon through 5‐HT 4 receptors (Tarn et al , 1994) whereas it induces contraction of longitudinal muscle strips of the ileum through 5‐HT 2B receptors (Borman & Burleigh, 1995). In in vivo studies, 5‐HT 4 receptors mediate several 5‐HT‐induced effects such as tachycardia in pigs (Villalón et al , 1991), forestomach hypomotility in sheep (Plaza et al , 1996c), gastric contractions in dogs (Bingham et al , 1995) and gastric emptying in both rats (Hegde et al , 1995) and dogs (Gullikson et al , 1993). Furthermore, gastrointestinal prokinetic benza‐mides, probably acting through 5‐HT 4 receptors, stimulate gastrointestinal contractile activity in man (Briejer et al , 1995) and dogs (Gullikson et al , 1993).…”