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Muscarinic Receptor‐Stimulated Phosphoinositide Turnover in Human SK‐N‐SH Neuroblastoma Cells: Differential Inhibition by Agents that Elevate Cyclic AMP
Author(s) -
Akil Mayada,
Fisher Stephen K.
Publication year - 1989
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.1471-4159.1989.tb08541.x
Subject(s) - forskolin , adenylate kinase , cholera toxin , cyclase , phospholipase c , inositol phosphate , muscarinic acetylcholine receptor , g protein , phosphodiesterase , endocrinology , biology , carbachol , medicine , pertussis toxin , cyclic nucleotide phosphodiesterase , phosphodiesterase inhibitor , receptor , chemistry , inositol , biochemistry , enzyme
The possibility that an increased intracellular concentration of cyclic AMP (cAMP) can regulate the extent of muscarinic receptor‐stimulated phosphoinositide (PPI) turnover in the human neuroblastoma cell line SK‐N‐SH was examined. Addition of either forskolin (or its water‐soluble nalog, L‐85,8051), theophylline, isobutylmethylxanthine, or Liolera toxin, agents that interact with either the catalytic unit of adenylate cyclase, cAMP phosphodiesterase, or the guanine nucleotide binding protein linked to adenylate cyclase activation, resulted in a 45–181% increase in cAMP concentration and a 27–70% inhibition of carbachol‐stimu‐lated inositol phosphate release. Through the use of digitonin‐permeabilized cells, the site of inhibition was localized to a step at, or distal to, the guanine nucleotide binding protein that regulates phospholipase C activity. In contrast, when intact SK‐N‐SH cells were exposed to prostaglandin E 1 , the ensuing increases in cAMP were not accompanied by an inhibition of stimulated PPI turnover. These differential effects of increased cAMP concentrations on stimulated PPI turnover may reflect the compartmentation of cAMP within SK‐N‐SH cells.