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PMID: 6246490 Published · ppublish English Journal Article

Mepacrine blocks beta-adrenergic agonist-induced desensitization in astrocytoma cells.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 77 ·No. 3 ·1980-03-00 ·Pages 1341-5

Mallorga P, Tallman JF, Henneberry RC, Hirata F, Strittmatter WT, Axelrod J

Abstract

C6 astrocytoma cells contain beta-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 beta-adrenergic receptors and by increased release of arachidonic aciid 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 beta-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 A2 in the local domain of the beta-adrenergic receptor may be involved in desensitization.

MeSH Terms
Adenylyl Cyclases/metabolism Animals Arachidonic Acids/metabolism Astrocytoma Cells, Cultured Isoproterenol/antagonists & inhibitors Melitten/pharmacology Phospholipases A/antagonists & inhibitors Phospholipases A2 Quinacrine/pharmacology Rats Receptors, Adrenergic/drug effects Receptors, Adrenergic, beta/drug effects,metabolism Tetracaine/pharmacology Tetradecanoylphorbol Acetate/pharmacology
Chemicals
Arachidonic Acids Receptors, Adrenergic Receptors, Adrenergic, beta Tetracaine Melitten Phospholipases A Phospholipases A2 Adenylyl Cyclases Quinacrine Isoproterenol Tetradecanoylphorbol Acetate
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Mallorga P
Tallman J F
Henneberry R C
Hirata F
Strittmatter W T
Axelrod J
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31 references, click to expand
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.77.3.1341
Published
1980-03-00
Pages
1341-5
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC348490
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.77.3.1341 PMC Full Text View journal details
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