The effect of subtype-selective muscarinic receptor antagonists on the cholinergic current in motoneurons of the lobster cardiac ganglion.
Muscarinic agonists evoke a voltage-dependent inward current in motoneurons of the lobster cardiac ganglion. In this study, a number of drugs, known to show muscarinic receptor subtype selectivity in mammals, were used to determine the pharmacological profile of the muscarinic receptor on lobster motoneurons. The neurons were held under voltage-clamp, and various concentrations of the antagonists were applied in the presence of 1 mM methacholine. From competition curves plotting agonist-induced current against antagonist concentration, the inhibitor affinity constant and the slope factor were determined. The rank order of potencies of antagonists having an effect was: atropine greater than pirenzepine greater than 4-DAMP greater than methoctramine greater than HHSiD = (R)-HHD greater than (S)-HHD. Neither AF-DX 116 nor gallamine were effective at concentrations as high as 10 mM. The M1-selective agonist McN-A-343 had no effect. Although this crustacean muscarinic receptor resembles the mammalian M1 muscarinic receptor because of its relatively high affinity for pirenzepine, the rank order of other subtype-specific antagonists does not otherwise resemble that of any of the pharmacologically defined muscarinic receptors in mammals. It may be preferable, therefore, to use a term such as 'pirenzepine-sensitive' muscarinic receptor rather than M1 or 'M1-like' for invertebrate muscarinic receptors with pharmacological characteristics like those reported here.
Freschi
J E
JE
Department of Neurology, Emory University School of Medicine, Atlanta, GA 30322.
D000109:Acetylcholine / Q000502:physiology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001667:Binding, Competitive; D005724:Ganglia / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D008322:Mammals; D016210:Methacholine Chloride / Q000494:pharmacology; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology*; D008121:Nephropidae; D010277:Parasympathomimetics / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology; D010890:Pirenzepine / Q000494:pharmacology; D011976:Receptors, Muscarinic / Q000187:drug effects* / Q000502:physiology
D010277:Parasympathomimetics; D010880:Piperidines; D011976:Receptors, Muscarinic; D016210:Methacholine Chloride; D010890:Pirenzepine; D001285:Atropine; C042375:4-diphenylacetoxy-1,1-dimethylpiperidinium; D000109:Acetylcholine