Opiate-induced Adenylyl Cyclase Superactivation Is Isozyme-specific
While acute activation of inhibitory G i/o -coupled receptors leads to inhibition of adenylyl cyclase, chronic activation of such receptors leads to an increase in cAMP accumulation. This phenomenon, observed in many cell types, has been referred to as adenylyl cyclase superactivation. At this stage...
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Published in | The Journal of biological chemistry Vol. 272; no. 8; pp. 5040 - 5047 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
United States
American Society for Biochemistry and Molecular Biology
21.02.1997
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Subjects | |
Online Access | Get full text |
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Summary: | While acute activation of inhibitory G i/o -coupled receptors leads to inhibition of adenylyl cyclase, chronic activation of such receptors leads to an increase in cAMP
accumulation. This phenomenon, observed in many cell types, has been referred to as adenylyl cyclase superactivation. At this
stage, the mechanism leading to adenylyl cyclase superactivation and the nature of the isozyme(s) responsible for this phenomenon
are largely unknown. Here we show that transfection of adenylyl cyclase isozymes into COS-7 cells results in an isozyme-specific
increase in AC activity upon stimulation ( e.g. with forskolin, ionomycin, or stimulatory receptor ligands). However, independently of the method used to activate specific
adenylyl cyclase isozymes, acute activation of the μ-opioid receptor inhibited the activity of adenylyl cyclases I, V, VI,
and VIII, while types II, IV, and VII were stimulated and type III was not affected. Chronic μ-opioid receptor activation
followed by removal of the agonist was previously shown, in transfected COS-7 cells, to induce superactivation of adenylyl
cyclase type V. Here we show that it also leads to superactivation of adenylyl cyclase types I, VI, and VIII, but not of type
II, III, IV, or VII, demonstrating that the superactivation is isozyme-specific. Not only were isozymes II, IV, and VII not
superactivated, but a reduction in the activities of these isozymes was actually observed upon chronic opiate exposure. These
results suggest that the phenomena of tolerance and withdrawal involve specific adenylyl cyclase isozymes. |
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Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2 |
ISSN: | 0021-9258 1083-351X |
DOI: | 10.1074/jbc.272.8.5040 |