5-HT2 receptors augment cholinergic nerve-mediated contraction of rat bronchi.
5-Hydroxytryptamine (5-HT) potentiated contractions of isolated rat bronchi evoked by electrical field stimulation (EFS). The degree of potentiation caused by 5-HT was dependent upon concentration of the amine present in the tissue bath. The effects of antagonists selective for different subtypes of the 5-HT receptor on potentiation of EFS-induced contractions by 5-HT were examined. Propranolol, a nonselective beta-adrenoceptor antagonist which can act as a 5-HT1 receptor antagonist, did not inhibit the effect of 5-HT on EFS-induced contractile responses. Similarly, 5-HT3 receptor antagonism with MDL 72222 or ICS 205-930, did not inhibit the facilitatory effects of 5-HT. However, ketanserin, mianserin and spiperone, 5-HT2 receptor antagonists, abolished the effects of 5-HT on EFS-induced responses. These latter results suggested that the potentiation was dependent upon activation of 5-HT2 receptors thus additional experiments were conducted using the 5-HT2 receptor agonist, alpha-methyl-5-hydroxytryptamine (alpha-Me-5-HT). alpha-Me-5-HT caused a concentration-dependent potentiation of EFS-induced contractile responses comparable to that observed with 5-HT. Concentrations of alpha-Me-5-HT that significantly potentiated EFS-induced contraction were essentially without effect on airway smooth muscle contraction elicited by exogenous acetylcholine. These results are consistent with a role for 5-HT2 receptor activation in mediating the facilitatory effects of 5-HT on cholinergic nerve-mediated responses in airways.
Szarek
J L
JL
Marshall University School of Medicine, Department of Pharmacology, Huntington, WV 25755-9310.
Zhang
J Z
JZ
Gruetter
C A
CA
D000818:Animals; D016084:Bronchoconstriction / Q000187:drug effects*; D004357:Drug Synergism; D004558:Electric Stimulation; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects*; D012701:Serotonin / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology*
D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D012701:Serotonin