Effects of nicotine on spontaneous contractions of isolated atria of toad (Bufo melanostictus).
In toad atria, nicotine, at low concentrations (6.1 X 10(-6) M to 6.2 X 10(-5) M), produced a negative inotropic effect, and, at high concentrations (6.2 X 10(-4) M to 3.1 X 10(-3) M), a positive inotropic effect. The negative inotropism was potentiated by physostigmine or neostigmine and was antagonized by atropine or hemicholinium-3. The positive inotropism remained unaffected by exposure to phenoxybenzamine, phentolamine, propranolol, guanethidine, bretylium, hexamethonium, hemicholinium-3 or pretreatment with 6-OHDA or tyramine tachyphylaxis. The positive inotropism was antagonized by ethylene diamine tetraethyl acetate, verapamil or calcium-free Ringer. Caffeine induced positive inotropic effects, which were antagonized only by EDTA, and remained unaffected by exposure to verapamil or calcium-free Ringer. These results suggest a cholinergic mechanism for the negative inotropism produced by low concentrations of nicotine and also that the primary site of action of nicotine, when added at high concentrations, is the sarcolemmal calcium channel of toad atria resulting in increased calcium influx. They further suggest that the nicotine-induced positive inotropism is not mediated through activation of atrial adrenoceptors, ganglionic activation, presynaptic liberation of acetylcholine or liberation of catecholamine from sympathetic nerve endings.
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002025:Bufonidae; D002110:Caffeine / Q000494:pharmacology; D004492:Edetic Acid / Q000494:pharmacology; D006426:Hemicholinium 3 / Q000494:pharmacology; D006584:Hexamethonium Compounds / Q000494:pharmacology; D006892:Hydroxydopamines / Q000494:pharmacology; D066298:In Vitro Techniques; D009200:Myocardial Contraction / Q000187:drug effects*; D009538:Nicotine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D016627:Oxidopamine; D010830:Physostigmine / Q000494:pharmacology; D014439:Tyramine / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
D006584:Hexamethonium Compounds; D006892:Hydroxydopamines; D006426:Hemicholinium 3; D002110:Caffeine; D009538:Nicotine; D001285:Atropine; D016627:Oxidopamine; D004492:Edetic Acid; D010830:Physostigmine; D014700:Verapamil; D014439:Tyramine