title: Involvement of M1-muscarinic receptors in the excitation of neocortical neurones by acetylcholine.
abstract: The technique of microelectrophoresis was used to investigate the cholinoceptor pharmacology of spontaneously active single neurones in the parietal cortex of the rat. Acetylcholine, carbachol and the selective M1-muscarinic receptor agonist, McN-A-343, were each potent excitants (rank order of apparent potency: carbachol greater than acetylcholine greater than McN-A-343). When measured in vitro, the apparent mobilities of carbachol and acetylcholine were similar although significantly less than that of McN-A-343, suggesting that the lower potencies of acetylcholine and McN-A-343 probably reflect a genuine biological phenomenon. In addition to excitation, carbachol also evoked biphasic (excitation/depression) and depressant responses. In contrast to the other cholinoceptor agonists, nicotine produced weak and inconsistent excitations. Excitatory responses to acetylcholine and carbachol were significantly attenuated by the selective M1-muscarinic receptor antagonist, pirenzepine, at a time when the excitatory response to McN-A-343 was also significantly reduced. Responses to phenylephrine were not diminished. On several cells an excitatory response to carbachol was converted to a depression by pirenzepine. These results suggest that the excitatory responses of cortical neurones to cholinoceptor agonists are mediated predominantly by M1-muscarinic receptors. The identity of the receptor mediating the depressant response to carbachol remains uncertain, although nicotinic cholinoceptors do not appear to be involved.
mesh_terms: D008455:(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride / Q000494:pharmacology; D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D002540:Cerebral Cortex / Q000166:cytology*; D008297:Male; D009474:Neurons / Q000187:drug effects*; D009538:Nicotine / Q000494:pharmacology; D010890:Pirenzepine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011976:Receptors, Muscarinic / Q000378:metabolism*; D013997:Time Factors
chemical_list: D011976:Receptors, Muscarinic; D010890:Pirenzepine; D008455:(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride; D009538:Nicotine; D002217:Carbachol; D000109:Acetylcholine