5‐HT receptor types in the rat ileum longitudinal muscle: focus on 5‐HT₂ receptors mediating contraction

Abstract

The 5-hydroxytryptamine (5-HT) receptor(s) that mediate(s) contraction of the rat ileum longitudinal muscle was studied.5-HT and a-methyl-5-HT equipotently induced contractions, whereas 5-methoxytryptamine and 2-methyl-5-HT (partial agonist) were less potent; this rank order of potency suggests involvement of a 5-HT 2 receptor. Neither tetrodotoxin nor atropine affected the contraction to 5-HT, suggesting a smooth muscle localization of these 5-HT 2 receptors. The presence of either a selective 5-HT 2B (SB 204741), 5-HT 3 (granisetron) or 5-HT 4 (SB 204070) antagonist, slightly affected the contractions to 5-HT. Thus, they were also included in the organ bath solution in all subsequent experiments in order to pharmacologically isolate the main contractile component. Using (if possible) 5-HT 2A receptorselective concentrations, ketanserin, ritanserin, metergoline, spiperone, mianserin, methiothepin, mesulergine, methysergide and cisapride all inhibited the contractions to 5-HT, causing a depression of the curve to 5-HT (i.e. surmountable antagonism was not observed with any of the above agents). Comparison of the affinities of these compounds for the various 5-HT 2 receptor subtypes revealed that the receptor involved in the contractions to 5-HT most closely resembles the 5-HT 2A receptor. However, cinanserin at a concentration expected to inhibit 5-HT 2A receptor-mediated effects, failed to affect the contractions to 5-HT.It is thus concluded that on the longitudinal smooth muscle of the rat ileum, at least a part of the contraction to 5-HT is mediated by 5-HT receptors resembling the 5-HT 2A receptor subtype.

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

“…Our results are consistent with earlier findings that a selective 5-HT 4 receptor antagonist, SB 204070 tended to enhance the contractions to 5-HT in the rat ileum. 34) In the corpus, the contractile responses to 5-HT were significantly inhibited by methysergide and ketanserin. However contractions were not inhibited by WAY-100635, GR127935, RS-127445 or SB-269970, suggesting the involvement of 5-HT 2A receptors in the contraction.…”

“…This discrepancy was also demonstrated between the ileum strips from guinea pigs 32) and rats. 33,34) In the rat ileum, 5-HT 4 receptors are located on the smooth muscles and promote cAMP formation, 2) resulting in the relaxation. Our results are consistent with earlier findings that a selective 5-HT 4 receptor antagonist, SB 204070 tended to enhance the contractions to 5-HT in the rat ileum.…”

Irritable Bowel Syndrome: Methods, Mechanisms, and Pathophysiology. Genetic epidemiology and pharmacogenetics in irritable bowel syndrome

“…The 5-HT 2A receptor gene is expressed in the brain, vagal nuclei, and the gut (11,74). The Ϫ1438 (G/A) polymorphism has been associated with anorexia nervosa, alcohol dependence, obesity, obsessive compulsive disorder, and seasonal affective disorder (33,86).…”

Exogenous Serotonin Regulates Proliferation of Interstitial Cells of Cajal in Mouse Jejunum Through 5-HT2B Receptors

“…11 Of the 7 classes of 5-HT receptors, 5-HT 1 , 5-HT 2 , 5-HT 3 , 5-HT 4 , and 5-HT 7 receptors are known to be expressed in the gastrointestinal tract and to affect gastrointestinal motor function. [12][13][14][15][16][17][18][19][20] The role of 5-HT in regulating gastrointestinal motility by mediating the transduction of luminal signals across the mucosa and by participating in enteric neurotransmission is well established. 21,22 There is however significant evidence, mostly from outside the gastrointestinal tract but also in studies on enteric nervous system development, that shows that 5-HT can also regulate cell survival and proliferation.…”