Evidence for a postsynaptic action of neostigmine on muscarinic receptors in the anococcygeus muscle of the rat.
In the rat anococcygeus muscle neostigmine induces atropine-sensitive, significant leftward displacements of the log concentration-response curves to both noradrenaline and 5-hydroxytryptamine. Responses to high K+ were also potentiated by neostigmine. However, high K+ elicited only small and irregular overflows of tritium from [3H]noradrenaline pre-incubated tissues, in contrast to the large overflow elicited by field stimulation. In addition guanethidine blocked responses to field stimulation but not those to high K+. This is consistent with the dose-related responses to high K+ being elicited postsynaptically. These results indicate that postsynaptic muscarinic receptors are involved in the potentiation by neostigmine of rat anococcygeus muscle responses to field stimulation or exogenous agonists, possibly by an action on receptor operated ion channels. Additional support for a postsynaptic site of action comes from the failure of neostigmine to potentiate tension responses to nerve or field stimulation in the chick expansor secundariorum, a muscle which is devoid of postsynaptic muscarinic receptors.
Smith
J A
JA
Department of Pharmacology and Therapeutics, University of Wales College of Medicine, Health Park, Cardiff, UK.
Spriggs
T L
TL
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002645:Chickens; D004558:Electric Stimulation; D006145:Guanethidine / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D009388:Neostigmine / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011976:Receptors, Muscarinic / Q000187:drug effects* / Q000378:metabolism; D012701:Serotonin / Q000494:pharmacology; D013569:Synapses / Q000187:drug effects
D011976:Receptors, Muscarinic; D012701:Serotonin; D009388:Neostigmine; D011189:Potassium Chloride; D001285:Atropine; D009638:Norepinephrine; D006145:Guanethidine