Mepacrine Blocks β -Adrenergic Agonist-Induced Desensitization in Astrocytoma Cells

C6astrocytoma cells contain β -adrenergic receptors coupled to adenylate cyclase. A 2-hr exposure to l-isoproterenol results in an 80% decrease in cyclic AMP production in response to a subsequent challenge by l-isoproterenol (desensitization). This loss in responsiveness is paralleled by a 20-30% d...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1980-03, Vol.77 (3), p.1341-1345
Main Authors: Mallorga, Pierre, Tallman, John F., Henneberry, Richard C., Hirata, Fusao, Strittmatter, Warren T., Axelrod, Julius
Format: Article
Language:English
Subjects:
Adenylyl Cyclases - metabolism
Agonists
Animals
Arachidonic Acids - metabolism
Astrocytoma
Biochemistry
Cell growth
Cell lines
Cells, Cultured
HeLa cells
Inurement
Isoproterenol - antagonists & inhibitors
Melitten - pharmacology
Methylation
Phospholipases A - antagonists & inhibitors
Phospholipases A2
Phospholipids
Quinacrine - pharmacology
Rats
Receptors
Receptors, Adrenergic - drug effects
Receptors, Adrenergic, beta - drug effects
Receptors, Adrenergic, beta - metabolism
Tetracaine - pharmacology
Tetradecanoylphorbol Acetate - pharmacology
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Summary:C6astrocytoma cells contain β -adrenergic receptors coupled to adenylate cyclase. A 2-hr exposure to l-isoproterenol results in an 80% decrease in cyclic AMP production in response to a subsequent challenge by l-isoproterenol (desensitization). This loss in responsiveness is paralleled by a 20-30% decrease in the apparent number of β -adrenergic receptors and by increased release of arachidonic acid into the medium. The increased release of arachidonic acid is caused by the action of phospholipase A2(phosphatide 2-acylhydrolase, EC 3.1.1.4) and corresponds to increased turnover of methylated phospholipids. Mepacrine and tetracaine, both inhibitors of this phospholipase A2, are able to block l-isoproterenol-induced desensitization of cyclic AMP production and the decrease in β -adrenergic receptors. Mellitin and phorbol ester, two activators of phospholipase A2, when preincubated with the cells cause a decreased cyclic AMP response of the cells to l-isoproterenol. These results suggest that the activation of phospholipase A2in the local domain of the β -adrenergic receptor may be involved in desensitization.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.77.3.1341