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Title: Norepinephrine-induced alteration in the coupling of. cap alpha. /sub 1/-adrenergic receptor occupancy to calcium efflux in rabbit aortic smooth muscle cells

Abstract

To determine whether ..cap alpha..-adrenergic desensitization of vascular smooth muscle is due to an alteration in ..cap alpha../sub 1/-adrenergic receptor coupling, the authors determined the relationship between receptor occupancy and maximal receptor-coupled Ca/sup 2 +/ efflux in cultured rabbit aortic smooth muscle cells (i) under basal conditions as defined by receptor inactivation with phenoxybenzamine and (ii) after 48 hr of exposure to several concentrations of 1-norepinephrine (NE). Neither phenoxybenzamine nor NE exposure caused a change in binding affinity for (/sup 3/H)prazosin or NE. Maximal (/sup 3/H)prazosin binding capacity and maximal NE-stimulated /sup 45/Ca/sup 2 +/ efflux decreased progressively with exposure of incubated cells to increasing concentrations of phenoxybenzamine or NE. An approximately 80% decrease in maximal (/sup 3/H)prazosin binding capacity caused by either phenoxybenzamine or NE resulted in complete loss of NE-stimulated /sup 45/Ca/sup 2 +/ efflux, indicating that under these conditions approximately 20% of ..cap alpha../sub 1/-adrenergic receptors are not coupled to the Ca/sup 2 +/ efflux. Under basal conditions, the relationship between maximal (/sup 3/H)prazosin binding capacity and maximal NE-stimulated /sup 45/Ca/sup 2 +/ efflux was markedly nonlinear, so that a near maximal response could be elicited by occupancy of only approximately 40% of the receptors. Thus, anmore » alteration in occupancy-response coupling at a step proximal to Ca/sup 2 +/ mobilization and/or influx, rather than a reduction in receptor number, is of primary importance in the process of agonist-induced ..cap alpha..-adrenergic receptor desensitization of vascular smooth muscle cells.« less

Authors:
;
Publication Date:
Research Org.:
Harvard Medical School, Boston, MA (United States)
OSTI Identifier:
5766756
Resource Type:
Journal Article
Journal Name:
Proc. Natl. Acad. Sci. U.S.A.; (United States)
Additional Journal Information:
Journal Volume: 83:6
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; CALCIUM 45; MEMBRANE TRANSPORT; SYMPATHOMIMETICS; RADIORECEPTOR ASSAY; INACTIVATION; MUSCLES; NORADRENALINE; PHYSIOLOGY; RABBITS; TRITIUM COMPOUNDS; ADRENAL HORMONES; ALKALINE EARTH ISOTOPES; ANIMALS; AUTONOMIC NERVOUS SYSTEM AGENTS; BETA DECAY RADIOISOTOPES; BETA-MINUS DECAY RADIOISOTOPES; CALCIUM ISOTOPES; CARDIOTONICS; CARDIOVASCULAR AGENTS; DAYS LIVING RADIOISOTOPES; DRUGS; EVEN-ODD NUCLEI; INTERMEDIATE MASS NUCLEI; ISOTOPE APPLICATIONS; ISOTOPES; LABELLED COMPOUNDS; MAMMALS; NEUROREGULATORS; NUCLEI; RADIOISOTOPES; TRACER TECHNIQUES; VERTEBRATES; 550601* - Medicine- Unsealed Radionuclides in Diagnostics

Citation Formats

Colucci, W S, and Alexander, R W. Norepinephrine-induced alteration in the coupling of. cap alpha. /sub 1/-adrenergic receptor occupancy to calcium efflux in rabbit aortic smooth muscle cells. United States: N. p., 1986. Web. doi:10.1073/pnas.83.6.1743.
Colucci, W S, & Alexander, R W. Norepinephrine-induced alteration in the coupling of. cap alpha. /sub 1/-adrenergic receptor occupancy to calcium efflux in rabbit aortic smooth muscle cells. United States. https://doi.org/10.1073/pnas.83.6.1743
Colucci, W S, and Alexander, R W. 1986. "Norepinephrine-induced alteration in the coupling of. cap alpha. /sub 1/-adrenergic receptor occupancy to calcium efflux in rabbit aortic smooth muscle cells". United States. https://doi.org/10.1073/pnas.83.6.1743.
@article{osti_5766756,
title = {Norepinephrine-induced alteration in the coupling of. cap alpha. /sub 1/-adrenergic receptor occupancy to calcium efflux in rabbit aortic smooth muscle cells},
author = {Colucci, W S and Alexander, R W},
abstractNote = {To determine whether ..cap alpha..-adrenergic desensitization of vascular smooth muscle is due to an alteration in ..cap alpha../sub 1/-adrenergic receptor coupling, the authors determined the relationship between receptor occupancy and maximal receptor-coupled Ca/sup 2 +/ efflux in cultured rabbit aortic smooth muscle cells (i) under basal conditions as defined by receptor inactivation with phenoxybenzamine and (ii) after 48 hr of exposure to several concentrations of 1-norepinephrine (NE). Neither phenoxybenzamine nor NE exposure caused a change in binding affinity for (/sup 3/H)prazosin or NE. Maximal (/sup 3/H)prazosin binding capacity and maximal NE-stimulated /sup 45/Ca/sup 2 +/ efflux decreased progressively with exposure of incubated cells to increasing concentrations of phenoxybenzamine or NE. An approximately 80% decrease in maximal (/sup 3/H)prazosin binding capacity caused by either phenoxybenzamine or NE resulted in complete loss of NE-stimulated /sup 45/Ca/sup 2 +/ efflux, indicating that under these conditions approximately 20% of ..cap alpha../sub 1/-adrenergic receptors are not coupled to the Ca/sup 2 +/ efflux. Under basal conditions, the relationship between maximal (/sup 3/H)prazosin binding capacity and maximal NE-stimulated /sup 45/Ca/sup 2 +/ efflux was markedly nonlinear, so that a near maximal response could be elicited by occupancy of only approximately 40% of the receptors. Thus, an alteration in occupancy-response coupling at a step proximal to Ca/sup 2 +/ mobilization and/or influx, rather than a reduction in receptor number, is of primary importance in the process of agonist-induced ..cap alpha..-adrenergic receptor desensitization of vascular smooth muscle cells.},
doi = {10.1073/pnas.83.6.1743},
url = {https://www.osti.gov/biblio/5766756}, journal = {Proc. Natl. Acad. Sci. U.S.A.; (United States)},
number = ,
volume = 83:6,
place = {United States},
year = {Sat Mar 01 00:00:00 EST 1986},
month = {Sat Mar 01 00:00:00 EST 1986}
}