Subtypes of muscarinic receptors in vagal inhibitory pathway to the lower esophageal sphincter of the opossum

Abstract

We assessed the characteristics of muscarinic neural transmission in the vagal inhibitory pathway to the lower esophageal sphincter (LES) of anesthetized opossums. LES relaxation was induced by electrical stimulation of the cervical vagus. Measurements were made of LES relaxation before and after intravenous administration of nicotinic (hexamethonium), serotonergic (5-Meo-DMT), nonselective muscarinic (atropine), and selective muscarinic (pirenzepine-M₁ and 4-DAMP-M₂) antagonists. The latency of LES relaxamethonium, but was not affected by 4-DAMP or 5-Meo-DMT. Given as concurrent intravenous infusions, hexamethonium, 5-Meo-DMT and 4-DAMP added to pirenzepine or atropine did not significantly increase LES relaxation latency above that caused by pirenzepine or atropine alone. None of the antagonists alone had a significant effect on percent LES relaxation. The combination of pirenzepine or 4-DAMP with hexamethonium and 5-Meo-DMT did not affect percent LES relaxation. The combination of atropine with hexamethonium and 5-Meo-DMT reduced LES relaxation to 18%. The combination of pirenzepine and 4-DAMP with hexamethonium and 5-Meo-DMT, however, had no effect on percent LES relaxation. We conclude that muscarinic participation in vagally induced LES relaxation exhibits two functional receptor subtypes: (1) M₁ receptors that determine LES relaxation latency and are antagonized by pirenzepine or atropine, and (2) non-M₁, non-M₂ receptors, (M_x receptors) that contribute to the magnitude of LES relaxation and are antagonized by atropine, but not by pirenzepine or 4-DAMP.