Reduction of a disulfide bond by β-adrenergic agonists: Evidence in support of a general "reductive activation" hypothesis for the mechanism of action of adrenergic agents

Douglas A. Peterson; Jon M. Gerrard

doi:10.1016/0306-9877(87)90007-7

Reduction of a disulfide bond by β-adrenergic agonists: Evidence in support of a general "reductive activation" hypothesis for the mechanism of action of adrenergic agents

Douglas A. Peterson, Jon M. Gerrard

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Abstract

β-adrenergic agonists, but not antagonists, were found to reduce the disulfide bond of 5,5′-dithiobis-2-nitrobenzoic acid (DTNB). The extent of DTNB reduction was proportional to the intrinsic activity for these agonists. The results suggest a novel mechanism for transmission of the signal when a β-adrenergic agonist occupies its receptor. We propose that β-adrenergic agonists exert their effects to activate the adenylate cyclase by reducing a disulfide bond in the receptor (R) or guanyl nucleotide binding protein (G) component of the adenylate cyclase complex leading to tight binding of GTP to G and activation of G.

Original language	English (US)
Pages (from-to)	45-49
Number of pages	5
Journal	Medical Hypotheses
Volume	22
Issue number	1
DOIs	https://doi.org/10.1016/0306-9877(87)90007-7
State	Published - Jan 1987
Externally published	Yes

Bibliographical note

Funding Information:
Grant support from MRC grant MA7396 is acknowledged. DAP is the recipient of a Veterans Administration Research Career Development Award and JMG is the recipient of an MRC Scientist Award. We are grateful to the technical assistance of R. Peterson, A. Crockett, A. Bress and B. McCoy and to Lori Devlin for typing this manuscript.

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title = "Reduction of a disulfide bond by β-adrenergic agonists: Evidence in support of a general {"}reductive activation{"} hypothesis for the mechanism of action of adrenergic agents",

abstract = "β-adrenergic agonists, but not antagonists, were found to reduce the disulfide bond of 5,5′-dithiobis-2-nitrobenzoic acid (DTNB). The extent of DTNB reduction was proportional to the intrinsic activity for these agonists. The results suggest a novel mechanism for transmission of the signal when a β-adrenergic agonist occupies its receptor. We propose that β-adrenergic agonists exert their effects to activate the adenylate cyclase by reducing a disulfide bond in the receptor (R) or guanyl nucleotide binding protein (G) component of the adenylate cyclase complex leading to tight binding of GTP to G and activation of G.",

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AU - Peterson, Douglas A.

AU - Gerrard, Jon M.

N1 - Funding Information: Grant support from MRC grant MA7396 is acknowledged. DAP is the recipient of a Veterans Administration Research Career Development Award and JMG is the recipient of an MRC Scientist Award. We are grateful to the technical assistance of R. Peterson, A. Crockett, A. Bress and B. McCoy and to Lori Devlin for typing this manuscript.

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AB - β-adrenergic agonists, but not antagonists, were found to reduce the disulfide bond of 5,5′-dithiobis-2-nitrobenzoic acid (DTNB). The extent of DTNB reduction was proportional to the intrinsic activity for these agonists. The results suggest a novel mechanism for transmission of the signal when a β-adrenergic agonist occupies its receptor. We propose that β-adrenergic agonists exert their effects to activate the adenylate cyclase by reducing a disulfide bond in the receptor (R) or guanyl nucleotide binding protein (G) component of the adenylate cyclase complex leading to tight binding of GTP to G and activation of G.

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Reduction of a disulfide bond by β-adrenergic agonists: Evidence in support of a general "reductive activation" hypothesis for the mechanism of action of adrenergic agents

Abstract

Bibliographical note

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