ROLE OF 5-HT2 RECEPTORS IN SEROTONIN-INDUCED CONTRACTIONS OF NONVASCULAR SMOOTH-MUSCLE

  • 1 January 1985
    • journal article
    • research article
    • Vol. 232  (3) , 770-774
Abstract
Vascular receptors responsible for serotonin-induced contraction are of the 5-HT2 subtype (site in brain cortical membranes that is preferentially radiolabeled by [3H]spiperone) whereas serotonin receptors mediating contraction in nonvascular smooth muscle were not extensively studied. In vitro studies using the 5-HT2 receptor antagonists ketanserin, LY53857 [6-mthyl-1-(methylethyl)ergoline-8-carboxylic acid, 2-hydroxy-1-methylpropylester[7]-2-butenedioate] and 1-(1-naphthyl)piperazine show that serontonin-induced contractions in the rat uterus and guinea pig trachea are also mediated by interaction with 5-HT2 receptors. Prazosin, but not the serotonin receptor antagonists, blocked serotonin-induced contractions in the rat vas deferens, indicating the .alpha.-adrenergic and not 5-HT, or 5-HT2 receptors mediate the contractile response to serotonin in this tissue. Because selective 5-HT2 receptor antagonists did not block contractions to serotonin in the rat fundus or guinea pig ileum, receptors in these gastrointestinal tissues are clearly not 5-HT2. Contractions to serotonin in the fundus but not in the ileum were blocked by certain antagonists [metergoline and 1-(-naphthyl)piperazine] demonstrating that the receptors involved in serotonin-induced contractions in the fundus are different from the ileum. Other differences between the fundus and ileum in serotonin-induced contractions include: the potency of serotonin is greater in the fundus than in theiluem; and the primary action of serotonin in the fundus is activation of a postsynaptic receptor on the smooth muscle whereas, in the ileum, serontonin exerts an indirect neuronal action ot effect acetylcholine release. At least 3 distinct serotonin receptors in smooth muslce, a 5-HT2 receptor in vascular, uterine and tracheal tissue, a different receptor in the fundus and yet a 3rdneuronal serotonergic receptor in the guinea-pig ileum were identified.