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Title: Alpha 2-adrenergic receptor stimulation of phospholipase A2 and of adenylate cyclase in transfected Chinese hamster ovary cells is mediated by different mechanisms

Abstract

The effect of alpha 2-adrenergic receptor activation on adenylate cyclase activity in Chinese hamster ovary cells stably transfected with the alpha 2A-adrenergic receptor gene is biphasic. At lower concentrations of epinephrine forskolin-stimulated cyclic AMP production is inhibited, but at higher concentrations the inhibition is reversed. Both of these effects are blocked by the alpha 2 antagonist yohimbine but not by the alpha 1 antagonist prazosin. Pretreatment with pertussis toxin attenuates inhibition at lower concentrations of epinephrine and greatly potentiates forskolin-stimulated cyclic AMP production at higher concentrations of epinephrine. alpha 2-Adrenergic receptor stimulation also causes arachidonic acid mobilization, presumably via phospholipase A2. This effect is blocked by yohimbine, quinacrine, removal of extracellular Ca2+, and pretreatment with pertussis toxin. Quinacrine and removal of extracellular Ca2+, in contrast, have no effect on the enhanced forskolin-stimulated cyclic AMP production. Thus, it appears that the alpha 2-adrenergic receptor in these cells can simultaneously activate distinct signal transduction systems; inhibition of adenylate cyclase and stimulation of phospholipase A2, both via G1, and potentiation of cyclic AMP production by a different (pertussis toxin-insensitive) mechanism.

Authors:
; ;  [1]
  1. (Univ. of Missouri-Columbia (USA))
Publication Date:
OSTI Identifier:
6057332
Resource Type:
Journal Article
Journal Name:
Molecular Pharmacology; (USA)
Additional Journal Information:
Journal Volume: 39:2; Journal ID: ISSN 0026-895X
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; CYCLASES; ENZYME ACTIVITY; LIPASES; RECEPTORS; BIOCHEMICAL REACTION KINETICS; SYMPATHOMIMETICS; AMP; CHO CELLS; INHIBITION; TOXINS; TRACER TECHNIQUES; TRITIUM COMPOUNDS; ANIMAL CELLS; ANTIGENS; AUTONOMIC NERVOUS SYSTEM AGENTS; CARBOXYLESTERASES; DRUGS; ENZYMES; ESTERASES; HYDROGEN COMPOUNDS; HYDROLASES; ISOTOPE APPLICATIONS; KINETICS; LYASES; MATERIALS; MEMBRANE PROTEINS; NUCLEOTIDES; ORGANIC COMPOUNDS; PROTEINS; REACTION KINETICS; TOXIC MATERIALS; 550201* - Biochemistry- Tracer Techniques

Citation Formats

Jones, S.B., Halenda, S.P., and Bylund, D.B. Alpha 2-adrenergic receptor stimulation of phospholipase A2 and of adenylate cyclase in transfected Chinese hamster ovary cells is mediated by different mechanisms. United States: N. p., 1991. Web.
Jones, S.B., Halenda, S.P., & Bylund, D.B. Alpha 2-adrenergic receptor stimulation of phospholipase A2 and of adenylate cyclase in transfected Chinese hamster ovary cells is mediated by different mechanisms. United States.
Jones, S.B., Halenda, S.P., and Bylund, D.B. Fri . "Alpha 2-adrenergic receptor stimulation of phospholipase A2 and of adenylate cyclase in transfected Chinese hamster ovary cells is mediated by different mechanisms". United States.
@article{osti_6057332,
title = {Alpha 2-adrenergic receptor stimulation of phospholipase A2 and of adenylate cyclase in transfected Chinese hamster ovary cells is mediated by different mechanisms},
author = {Jones, S.B. and Halenda, S.P. and Bylund, D.B.},
abstractNote = {The effect of alpha 2-adrenergic receptor activation on adenylate cyclase activity in Chinese hamster ovary cells stably transfected with the alpha 2A-adrenergic receptor gene is biphasic. At lower concentrations of epinephrine forskolin-stimulated cyclic AMP production is inhibited, but at higher concentrations the inhibition is reversed. Both of these effects are blocked by the alpha 2 antagonist yohimbine but not by the alpha 1 antagonist prazosin. Pretreatment with pertussis toxin attenuates inhibition at lower concentrations of epinephrine and greatly potentiates forskolin-stimulated cyclic AMP production at higher concentrations of epinephrine. alpha 2-Adrenergic receptor stimulation also causes arachidonic acid mobilization, presumably via phospholipase A2. This effect is blocked by yohimbine, quinacrine, removal of extracellular Ca2+, and pretreatment with pertussis toxin. Quinacrine and removal of extracellular Ca2+, in contrast, have no effect on the enhanced forskolin-stimulated cyclic AMP production. Thus, it appears that the alpha 2-adrenergic receptor in these cells can simultaneously activate distinct signal transduction systems; inhibition of adenylate cyclase and stimulation of phospholipase A2, both via G1, and potentiation of cyclic AMP production by a different (pertussis toxin-insensitive) mechanism.},
doi = {},
journal = {Molecular Pharmacology; (USA)},
issn = {0026-895X},
number = ,
volume = 39:2,
place = {United States},
year = {1991},
month = {2}
}