Contractile serotonergic receptor in rat stomach fundus.
Serotonin (5HT) is a potent agonist in contracting the rat stomach fundus although the nature of the receptor mediating the response has not been established. The present study was designed to explore the possibility that 5HT-induced contractions in the rat stomach fundus were mediated by interaction with receptors identical with either 5HT1A, 5HT1B or 5HT1C binding sites or 5HT3 receptors. Contractile concentration-response curves for several 5HT agonists [5-carboxamidotryptamine, TR3369, MK212, quipazine, RU 24969, 8-hydroxy-2-(di-n-propylamino)tetralin, TVXQ7821 and BEA 1654CL] were obtained in the rat stomach fundus. However, neither the potency nor maximum response of these agonists in contracting the rat stomach fundus correlated with the affinity of agonists at 5HT1A, 5Ht1B or 5HT1C binding sites. These agonists were interacting with 5HT receptors in the fundus based on the ability of 1-(1-naphthyl) piperazine (10(-7) M) to antagonize the contractile response of the relatively potent agonists. TVXQ7821 and BEA 1654Cl did not produce a marked contractile response in the fundus and also did not antagonize the contractile response to 5HT, suggesting that these agents have little, if any, affinity for the serotonergic receptor-mediating contraction in the fundus. The putative 5HT1A-selective receptor antagonists, WB4101 and spiroxatrine, did not block 5HT-induced contractions in the rat stomach fundus in concentrations consistent with their affinity at 5HT1A binding sites. The nonselective 5HT1A and 5HT1B receptor antagonist, cyanopindolol, also did not block 5HT-induced contractions in the rat stomach fundus.(ABSTRACT TRUNCATED AT 250 WORDS)
Cohen
M L
ML
Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana.
Fludzinski
L A
LA
D000818:Animals; D005748:Gastric Fundus / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology*
D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D012701:Serotonin