Functional evidence of excitatory M1 receptors in the rabbit airway.
The effect of vagally and acetylcholine (ACh)-induced bronchoconstrictions was assessed by an increase in the slowly adapting pulmonary stretch receptor (SAR) activity during both inflation and deflation and the rise in total lung resistance (R(L)). Those responses were compared before and after pirenzepine (PZ, M1 selective) with or without propranolol (a beta adrenoreceptor blocker), gallamine (M2 selective), 4-DAMP (M3 selective), hexamethonium (C6, a ganglion blocker) and atropine (a nonselective muscarinic receptor antagonist). The SAR activity was recorded from the cut left vagus nerve, whereas the right vagus nerve was cut and stimulated electrically. Experiments were performed in anesthetized, artificially ventilated rabbits. Vagal stimulation (5-20 Hz, 13 V, 0.2 msec) for 30 sec and ACh injection (1 and 3 microg/kg) caused bronchoconstriction in a frequency- and dose-dependent manner. At the treatment with PZ (3-30 microg/kg) in both propranolol-untreated and -treated animals, vagally mediated bronchoconstriction was blocked by this M1 receptor blocker at 10 microg/kg, whereas ACh-induced bronchoconstriction was not significantly altered by any dose of PZ. Gallamine (3-30 microg/kg) had no significant effect on vagally and ACh-induced bronchoconstrictions, which were completely blocked by atropine (2 mg/kg). Three micrograms of 4-DAMP augmented the SAR and R(L) responses to vagal stimulation but inhibited those responses to ACh injection. 4-DAMP at 10 to 30 microg/kg dose-dependently inhibited both vagally and ACh-induced bronchoconstrictions. C6 (20 mg/kg) abolished vagally mediated bronchoconstriction but had no significant effect on ACh-induced bronchoconstriction. These results suggest that M1 receptors function as the excitatory receptors in the rabbit airway.
Matsumoto
S
S
Department of Physiology, Nippon Dental University, School of Dentistry at Tokyo, Japan.
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D016084:Bronchoconstriction / Q000187:drug effects*; D005260:Female; D005703:Gallamine Triethiodide / Q000494:pharmacology; D008297:Male; D008465:Mechanoreceptors / Q000187:drug effects; D010890:Pirenzepine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011817:Rabbits; D043643:Receptor, Muscarinic M1; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000502:physiology*; D014630:Vagus Nerve / Q000502:physiology
D043643:Receptor, Muscarinic M1; D011976:Receptors, Muscarinic; D010890:Pirenzepine; D001285:Atropine; D011433:Propranolol; D000109:Acetylcholine; D005703:Gallamine Triethiodide