Plasma membrane-associated nucleoside diphosphate kinase (nm23) in the heart is regulated by beta-adrenergic signaling.
Br J Pharmacol
; 140(6): 1019-26, 2003 Nov.
Article
en En
| MEDLINE
| ID: mdl-14559858
ABSTRACT
1. Receptor-independent activation of heterotrimeric G proteins by plasma membrane-associated nucleoside diphosphate kinase (NDPK) has been demonstrated in vivo, and elevated levels of NDPK were found in purified sarcolemmal membranes of patients with end-stage heart failure. 2. Among 22 consecutive patients with chronic heart failure who underwent cardiac transplantation, those treated with a beta-blocker (n=8) had a 65% lower NDPK content and activity in the cardiac sarcolemma, compared to patients with similar base line characteristics who had no beta-blocker therapy (n=14). 3. The lower NDPK was associated with a reduced NDPK-dependent, Gi-mediated inhibition of adenylyl cyclase activity, as assessed by in vitro measurement of adenylyl cyclase activity in the presence of GDP or its kinase-resistant analog guanosine 5'-O-(2-thio)diphosphate (GDPbetaS). 4. We further tested whether treatment with a beta-adrenergic agonist would induce an increase in sarcolemmal NDPK. Rats treated with isoproterenol developed myocardial hypertrophy, and NDPK in the sarcolemma rose by 60% during 14 days of treatment. The beta-blocker propranolol prevented both effects. When hypertrophy was induced with thyroid hormone, NDPK did not increase. 5. In conclusion, chronic activation of beta-adrenergic receptors increases the binding of NDPK to cardiac sarcolemma, where it may activate heterotrimeric G proteins.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Sarcolema
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Nucleósido-Difosfato Quinasa
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Antagonistas Adrenérgicos beta
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Miocardio
Tipo de estudio:
Prognostic_studies
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Risk_factors_studies
Límite:
Adult
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Aged
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Animals
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Br J Pharmacol
Año:
2003
Tipo del documento:
Article
País de afiliación:
Alemania