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Effects of Muscarinic Agonists and Depolarizing Agents on Inositol Monophosphate Accumulation in the Rabbit Vagus Nerve
Author(s) -
Sierro Christian D.,
Vitus Josée,
Dunant Yves
Publication year - 1992
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1992.tb09392.x
Subject(s) - pirenzepine , muscarinic acetylcholine receptor , carbachol , endocrinology , medicine , oxotremorine , chemistry , inositol , inositol phosphate , muscarinic acetylcholine receptor m3 , muscarinic acetylcholine receptor m1 , depolarization , receptor , biology , biochemistry
The effects of muscarinic agonists and depolarizing agents on inositol phospholipid hydrolysis in the rabbit vagus nerve were assessed by the measurement of [ 3 H]inositol monophosphate production in nerves that had been preincubated with [ 3 H]inositol. After 1 h of drug action, carbachol, oxotremorine, and arecoline increased the inositol monophosphate accumulation, though the maximal increase induced by these agonists differed. Addition of the muscarinic antagonists atropine or pirenzepine shifted the carbachol dose‐response curves to the right, without decreasing the carbachol maximal stimulatory effects. The K B for pirenzepine was 35 n M , which is characteristic of muscarinic high‐affinity binding sites coupled to phosphoinositide turnover and often associated with the M 1 receptor subtype. On the other hand, agents known to depolarize or to increase the intracellular Ca 2+ concentration, e.g., elevated extracellular K + , ouabain, Ca 2+ , and the Ca 2+ ionophore A23187, also increased inositol monophosphate accumulation. These effects were not mediated by the release of acetylcholine, as suggested by the fact that they could not be potentiated by the addition of physostigmine nor inhibited by the addition of atropine. The Ca 2+ ‐channel antagonist Cd 2+ , also known to inhibit the Na + /Ca 2+ exchanger, was able to block the effects of K + and ouabain, but did not alter those of carbachol. These results suggest that depolarizing agents increase inositol monophosphate accumulation in part through elevation of the intracellular Ca 2+ concentration and that muscarinic receptors coupled to phosphoinositide turnover are present along the trunk of the rabbit vagus nerve.