Abstract |
We have shown previously in dogs with right heart failure that the reduction of myocardial beta- adrenoceptor density occurs only in the failing right ventricle, while cardiac inotropic responses to beta- adrenergic stimulation are reduced in both the right and left ventricles. The purpose of the present study was to determine whether a post-receptor defect in the guanine nucleotide-binding regulatory proteins ( G-proteins) existed which would explain, at least in part, the adrenergic subsensitivity in both ventricles of the heart failure dogs. Using both immunoblotting technique and the bacterial toxin-mediated ADP ribosylation assays, we found that the stimulatory G-protein (Gs) was reduced in both ventricles of the heart failure dogs. In contrast, there were no changes in the inhibitory G-protein (Gi). In addition, receptor subtype analysis showed that only beta(1)-adrenoceptors were reduced in the failing right ventricle of the heart failure animals. This study demonstrated that the reduction of beta- adrenoceptors in right heart failure was chamber-specific whereas the reduction of Gs was non-selective, occurring in both ventricles of right heart failure dogs. The findings further suggest that the reduction of Gs probably was caused by systemic neurohormonal activation, independent of local ventricular stress.
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Authors | L P Lai, M Suematsu, H Elam, C S Liang |
Journal | European journal of pharmacology
(Eur J Pharmacol)
Vol. 309
Issue 2
Pg. 201-8
(Aug 08 1996)
ISSN: 0014-2999 [Print] Netherlands |
PMID | 8874140
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Phosphorus Isotopes
- Receptors, Adrenergic, beta
- Virulence Factors, Bordetella
- Adenosine Diphosphate
- Cholera Toxin
- Pertussis Toxin
- GTP-Binding Proteins
- Adenylyl Cyclases
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Topics |
- Adenosine Diphosphate
(metabolism)
- Adenylyl Cyclases
(metabolism)
- Animals
- Blotting, Western
- Cholera Toxin
(metabolism)
- Dogs
- GTP-Binding Proteins
(metabolism)
- Heart Failure
(metabolism)
- Heart Ventricles
(enzymology, metabolism, physiopathology)
- Pertussis Toxin
- Phosphorus Isotopes
- Receptors, Adrenergic, beta
(classification, metabolism)
- Virulence Factors, Bordetella
(metabolism)
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