The interaction of hemicholinium-3 (HC-3) with cholinomimetics and atropine.
In either spontaneously beating or electrically driven atrial preparations of the guinea pig HC-3 (0.01-1 mM) inhibited negative inotropic responses to acetylcholine or carbachol. Although there was a parallel rightwards shift of the log concentration--response curves for acetylcholine or carbachol and no depression of the maximal response the type of antagonism was not competitive as the relationship between dose ratio -- 1) and concentration of HC-3 was not linear over the whole range investigated. A lesser degree of antagonism than expected for a competitive antagonist was observed with higher concentrations of HC-3. HC-3 was a more effective antagonist of responses to carbachol than to acetylcholine and pretreatment of animals with dyflos did not modify this difference. In addition, HC-3 was found to antagonize the inhibitory action of atropine on responses to acetylcholine and to a lesser extent carbachol. The results can be explained in terms of the interaction of HC-3 at a regulatory site distinct from the binding sites for cholinomimetics and atropinics. Interaction of HC-3 at the postulated site produces a noncompetitive antagonism of both agonists and competitive antagonists by modifying the affinities of the compounds for their respective binding sites.
D000818:Animals; D016275:Atrial Function; D001285:Atropine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002217:Carbachol / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004558:Electric Stimulation; D006168:Guinea Pigs; D006325:Heart Atria / Q000187:drug effects; D006426:Hemicholinium 3 / Q000494:pharmacology*; D066298:In Vitro Techniques; D007531:Isoflurophate / Q000494:pharmacology; D008464:Mecamylamine / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects*; D010277:Parasympathomimetics / Q000494:pharmacology*; D014326:Tropanes / Q000037:antagonists & inhibitors
D010277:Parasympathomimetics; D014326:Tropanes; D007531:Isoflurophate; D006426:Hemicholinium 3; D008464:Mecamylamine; D001285:Atropine; D002217:Carbachol