title: A comparison between mechanisms of action of different nicotinic blocking agents on rat submandibular ganglia.
abstract: The blocking properties of tubocurarine, decamethonium, hexamethonium and trimetaphan on nicotinic agonists applied by repetitive ionophoretic pulses were examined in rat submandibular ganglion cells using a two-microelectrode voltage-clamp technique at 30 degrees C. Hexamethonium, a proposed slowly dissociating, open-channel blocker at concentrations of 2-20 microM did not produce a 'use-dependent' run-down of responses, but its antagonism was clearly dependent on membrane potential. The voltage-dependent reduction of agonist response by hexamethonium was not dependent on the nature of agonist used. Similar results were obtained with acetylcholine (ACh) and carbamylcholine (CCh) ionophoresis. (+)-Tubocurarine (5 microM) and decamethonium (10 microM) produced 'use-dependent' run-down of agonist responses which became more pronounced at higher frequency and as the cell was hyperpolarized, consistent with open-channel blockade. In contrast, trimetaphan (2.5 microM), a receptor antagonist did not cause 'use-dependent' run-down of responses. Hence, the antagonism produced by hexamethonium, unlike tubocurarine and decamethonium, could not be accounted for in terms of open-channel blockade but requires an alternative mechanism, the nature of which is discussed.
mesh_terms: D000109:Acetylcholine / Q000037:antagonists & inhibitors; D000818:Animals; D002217:Carbachol / Q000037:antagonists & inhibitors; D005260:Female; D005726:Ganglia, Parasympathetic / Q000187:drug effects*; D005730:Ganglionic Blockers / Q000494:pharmacology*; D018738:Hexamethonium; D006584:Hexamethonium Compounds / Q000494:pharmacology; D066298:In Vitro Techniques; D007478:Iontophoresis; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D005730:Ganglionic Blockers; D006584:Hexamethonium Compounds; D018738:Hexamethonium; D002217:Carbachol; D000109:Acetylcholine