Pharmacological Characterization of 5-Hydroxytryptamine-Receptor Subtypes in Circular Muscle from the Rat Stomach

Abstract

It is generally accepted that gastric emptying is regulated by the coordination of the proximal and distal stomach motilities. 5-HT has proven to be an important mediator of gastrointestinal motility.1,2) The stimulation of 5-HT 1B/1D receptors induces gastric accommodation in humans 3) and dogs, 4) and delays gastric emptying in humans. 5,6) The blockade of 5-HT 3 receptors inhibits gastrointestinal motility in humans. 7) In addition, the stimulation of 5-HT 4 receptors elicits gastrointestinal contractile activity and increases the rate of gastric emptying in humans 8,9) and dogs. [10][11][12] With regard to gastric smooth muscle activity, it is generally accepted that the 5-HT 1B/1D and 5-HT 7 receptors are relaxant whereas the 5-HT 2 , 5-HT 3 and 5-HT 4 receptors are contractile. Although the gastric contractility of 5-HT has been reported in a variety of species and stomach regions, regional and functional differences of 5-HT-receptor subtypes have been fully investigated only in the guinea pig stomach. [13][14][15][16] In the guinea pig stomach, the fundus presents the relaxant 5-HT 1 receptors and the contractile 5-HT 2 and 5-HT 3 receptors, the corpus presents the relaxant 5-HT 1 receptors and the contractile 5-HT 3 and 5-HT 4 receptors, and the antrum presents the contractile 5-HT 2 , 5-HT 3 and 5-HT 4 receptors. However, the in vivo studies for examining gastric motility and gastric emptying using guinea pigs are limited. On the other hand, the rat is widely used as in vivo models to study gastric motility [17][18][19] and gastric emptying rate. [20][21][22] The stimulation of 5-HT 2 receptors increases gastric motility, 17) the blockade of 5-HT 3 receptors accelerates gastric emptying, 20) and the stimulation of 5-HT 4 receptors increases gastric motility 18) and accelerates gastric emptying. 20,21) In in vitro, pharmacological characterization of the contractile response to 5-HT in the rat stomach regions still remains unclear, except for the contractile 5-HT 2B receptors in longitudinal muscle strips of the fundus. [23][24][25] The present study was, therefore, designed to provide further information regarding functions of 5-HT receptor subtypes in circular muscle strips from the antrum, corpus and fundus of the rat stomach. MATERIALS AND METHODSChemicals Carbachol (CCh), atropine sulfate monohydrate and tetrodotoxin (TTX) were purchased from Wako Pure Chemicals (Osaka, Japan). 5-Hydroxytryptamine hydrochloride (5-HT), methysergide maleate, ketanserin tartrate and SB-269970 (selective 5-HT 7 receptor antagonist) were purchased from Sigma (St. Louis, MO, U.S.A.). WAY-100635 maleate (selective 5-HT 1A receptor antagonist), GR127935 hydrochloride (5-HT 1B/1D receptor antagonist) and cinanserin hydrochloride (selective 5-HT 2 receptor antagonist) were purchased from Tocris Cookson (Ellisville, MO, U.S.A.). RS-127445 (selective 5-HT 2B receptor antagonist), ondansetron (selective 5-HT 3 receptor antagonist) and SB-203186 (selective 5-HT 4 receptor antagonist) were synthesized at Pfizer Inc. All the drugs...

Cyproheptadine: A Potentially Effective Treatment for Functional Gastrointestinal Disorders in Children

“…40,41 Animal studies have shown that fundic contraction and relaxation of the stomach are regulated by 5-HT via 5-HT2A and 5-HT2B receptors as reported in rats, 42 guinea pigs, 43 and chickens, 44 as well as in the antrum in dogs. 11,45 Stimulation of the 5-HT2 receptor in dogs induced lower esophageal sphincter contractions, which were later inhibited by cyproheptadine.…”

Characteristics of 5-Hydroxytryptamine Receptors Involved in Contraction of Feline Ileal Longitudinal Smooth Muscle

“…A number of studies have characterized 5-HT-induced muscle contraction or relaxation responses and enhanced secretion in the GI tract via a multiplicity of 5-HT receptor subtypes [5,[9][10][11][12][13]. For example, in ferrets, 5-HT1 and 5-HT3 receptors mediate contraction, whereas in piglets, 5-HT1 receptors mediate the contraction in the ileum.…”

“…For example, in ferrets, 5-HT1 and 5-HT3 receptors mediate contraction, whereas in piglets, 5-HT1 receptors mediate the contraction in the ileum. In addition, 5-HT2 receptors mediate contraction and 5-HT4 receptors mediate relaxation in the rat stomach [11]. 5-HT1 and 5-HT2 receptors mediate contractions and 5-HT4 receptors mediate the relaxation in the ileum [5,12].…”

“…5-HT1 and 5-HT2 receptors mediate contractions and 5-HT4 receptors mediate the relaxation in the ileum [5,12]. In chickens, 5-HT1-and 5-HT2-like receptors mediate the contractions in the ileum [11]. In Suncus murinus, 5-HT2 and 5-HT3 receptors mediate contraction in the ileum [9], while 5-HT3 receptor mediates the contraction in mouse ileum [13].…”

“…5-HT4-like receptors mediate the relaxation of human colon [14]. In such studies, guinea-pig, rat, mouse, ferret, chicken and human have been widely used [5,[9][10][11][12][13][14]. However, the effect of 5-HT on the regulation of intestinal contraction or which 5-HT receptor is involved in the 5-HT-elicited response has not been established in isolated feline intestine.…”