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Title: Mr 40,000 and Mr 39,000 pertussis toxin substrates are increased in surgically denervated dog ventricular myocardium

To test the general hypothesis that cardiac innervation may participate in myocardial G protein regulation, we examined the effects of complete intrapericardial surgical denervation or sham operation in dogs. In particulate fractions of dog left ventricular (LV) myocardium harvested 28-33 days after denervation or sham operation, Mr 40,000 and Mr 39,000 pertussis toxin-sensitive substrates (G proteins) were increased by 31% (1.31 +/- 0.084 vs 1.00 +/- 0.058 OD, arbitrary units, p less than 0.01) and 40% (1.40 +/- 0.117 vs. 1.000 +/- 0.084 OD, arbitrary units, p less than 0.02), respectively, as compared with sham-operated controls. The Mr 40,000 pertussis toxin-sensitive band comigrated with a pertussis toxin-sensitive substrate in human erythrocyte membranes known to contain an alpha Gi species. In these same preparations basal, GTP and GppNHp stimulated adenylate cyclase activities were decreased in denervated heart by 20, 26, and 19%, respectively, consistent with increased activity of an inhibitory G protein. In contrast, Gs function was not altered, because cyc(-) membranes reconstituted with membrane extracts and fluoride and beta-receptor-stimulated adenylate cyclase activity were not different between groups. Furthermore, adenylate cyclase catalytic subunit function as assessed with forskolin and manganese stimulation was not different between preparations of control and denervated heart.more » We conclude that in preparations of surgically denervated dog myocardium Mr 40,000 and Mr 39,000 pertussis toxin-sensitive G proteins are increased by 31 and 40%, respectively, and that functional alterations in adenylate cyclase activity exist, consistent with increased inhibitory G-protein function.« less
Authors:
; ; ; ; ;  [1]
  1. (Univ. of Utah School of Medicine, Salt Lake City (USA))
Publication Date:
OSTI Identifier:
5272249
Resource Type:
Journal Article
Resource Relation:
Journal Name: Journal of Cardiovascular Pharmacology; (United States); Journal Volume: 17:4
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; CYCLASES; ENZYME ACTIVITY; MYOCARDIUM; BIOCHEMISTRY; PROTEINS; BIOSYNTHESIS; CATECHOLAMINES; CELL MEMBRANES; DOGS; ERYTHROCYTES; FLUORIDES; HEART; IN VITRO; INHIBITION; MAN; MANGANESE; NERVE CELLS; PHOSPHORUS ISOTOPES; TRACER TECHNIQUES; AMINES; ANIMAL CELLS; ANIMALS; AROMATICS; BIOLOGICAL MATERIALS; BLOOD; BLOOD CELLS; BODY; BODY FLUIDS; CARDIOVASCULAR SYSTEM; CELL CONSTITUENTS; CHEMISTRY; ELEMENTS; ENZYMES; FLUORINE COMPOUNDS; HALIDES; HALOGEN COMPOUNDS; HYDROXY COMPOUNDS; ISOTOPE APPLICATIONS; ISOTOPES; LYASES; MAMMALS; MATERIALS; MEMBRANES; METALS; MUSCLES; ORGANIC COMPOUNDS; ORGANS; PHENOLS; POLYPHENOLS; PRIMATES; SOMATIC CELLS; SYNTHESIS; TRANSITION ELEMENTS; VERTEBRATES 550201* -- Biochemistry-- Tracer Techniques