Modification of the effects of muscarinic agonists by reversible and irreversible anticholinesterase compounds in the guinea pig atrium.
The cholinergic agonists acetylcholine (ACh), carbamylcholine and methacholine were found to be equieffective in reducing the force of left atrial contraction, but to differ in their ability to shorten the action potential duration. The irreversible cholinesterase inhibitor soman had no effect on the actions of the non-hydrolyzable agonist carbamylcholine, but potentiated the actions of ACh. The reversible inhibitor edrophonium both potentiated and antagonized the effects of ACh. It antagonized the effects of carbamylcholine and after atrial cholinesterase was inhibited with soman it also antagonized the effects of ACh. Its anticholinesterase action and inhibitory action at the muscarinic receptor were confirmed in separate studies. Edrophonium is approximately 12 times more potent as an anticholinesterase than it is in blocking the muscarinic receptor. However, some actions of edrophonium cannot be explained in the context of its anticholinergic and antiesterase actions. Thus it increases the force of atrial contraction and antagonizes the negative inotropy due to soman. An inhibitory effect on an outward K+ current may be involved. The difference in the ability of the three cholinergic agonists to shorten the action potential may also be related to differences in efficacy at this K+ channel.
D000109:Acetylcholine / Q000494:pharmacology*; D000110:Acetylcholinesterase / Q000378:metabolism; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D016275:Atrial Function; D002217:Carbachol / Q000494:pharmacology*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004491:Edrophonium / Q000494:pharmacology; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D016210:Methacholine Chloride; D008688:Methacholine Compounds / Q000494:pharmacology*; D009200:Myocardial Contraction / Q000187:drug effects; D011813:Quinuclidinyl Benzilate / Q000378:metabolism; D011950:Receptors, Cholinergic / Q000187:drug effects / Q000378:metabolism; D012999:Soman / Q000494:pharmacology
D002800:Cholinesterase Inhibitors; D008688:Methacholine Compounds; D011950:Receptors, Cholinergic; D016210:Methacholine Chloride; D011813:Quinuclidinyl Benzilate; D004491:Edrophonium; D002217:Carbachol; D012999:Soman; D000110:Acetylcholinesterase; D000109:Acetylcholine