Kinetic studies on muscarinic antagonist-agonist competition.
The kinetics of the association and dissociation of the radiolabeled high affinity muscarinic antagonist N-[3H]methyl-4-piperidinyl benzilate was studied with the receptor from smooth muscle. Neither the agonists carbamylcholine and oxotremorine nor the antagonist atropine did influence the dissociation rate (k-2) of the receptor . antagonist complex. Binding of the antagonist (A) takes place in two consecutive steps: (formula: see text). Agonists did not seem to influence the dissociation constant (k-1/k+1) of the first binding step, while atropine caused a large increase in this constant. These results indicate that while antagonist-antagonist competition can be explained in terms of competition for the free receptor (R), antagonist-agonist competition cannot be fitted with such a simple model.
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001561:Benzilates / Q000378:metabolism*; D001667:Binding, Competitive; D002217:Carbachol / Q000494:pharmacology; D007421:Intestine, Small / Q000378:metabolism; D007700:Kinetics; D008297:Male; D009130:Muscle, Smooth / Q000378:metabolism*; D010095:Oxotremorine / Q000494:pharmacology; D010276:Parasympatholytics / Q000378:metabolism*; D010880:Piperidines / Q000378:metabolism*; D051381:Rats; D011950:Receptors, Cholinergic / Q000378:metabolism*; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000378:metabolism*
D001561:Benzilates; D010276:Parasympatholytics; D010880:Piperidines; D011950:Receptors, Cholinergic; D011976:Receptors, Muscarinic; D010095:Oxotremorine; D001285:Atropine; D002217:Carbachol; C020407:enpiperate