Alpha 1 adrenoceptor mediated signal transduction in neonatal rat ventricular myocytes: effects of prolonged hypoxia and reoxygenation.
Cardiovasc Res
; 25(7): 609-16, 1991 Jul.
Article
em En
| MEDLINE
| ID: mdl-1655268
ABSTRACT
STUDY OBJECTIVE:
The aim was to study the effects of prolonged hypoxia and reoxygenation on alpha 1 adrenoceptors and inositol phosphate accumulation in neonatal rat ventricular myocytes maintained in culture for 6-8 d.DESIGN:
Neonatal rat ventricular myocytes were subjected to 2 h hypoxia followed by 2 h reoxygenation. Cells were harvested at various times during hypoxia and after reoxygenation and measurements of alpha 1 adrenoceptor density and affinity and determinations of basal and (-)-noradrenaline stimulated inositol phosphate accumulation were carried out. EXPERIMENTALMATERIAL:
A neonatal rat ventricular myocyte preparation almost completely free of contaminating non-myocytes was used. Cells were grown in serum containing medium for 5 d before experiments were performed. alpha 1 Adrenoceptors were measured using the radioligand 125I-HEAT and inositol phosphates were measured by anion exchange chromatography after incubation with 1 microM (-)-noradrenaline for 5 min. MEASUREMENTS AND MAINRESULTS:
Hypoxia resulted in an increase in alpha 1 adrenoceptor density which was reversed by reoxygenation. There were no changes in antagonist affinity. (-)-Noradrenaline stimulated inositol phosphate production was increased at 1 h hypoxia but declined to control levels after 2 h hypoxia, while basal levels increased significantly at this time. This pattern was similar for all inositol phosphates measured inositol-1-phosphate, inositol bisphosphate, and the putative second messenger, inositol trisphosphate. Displacement by (-)-noradrenaline of 125I-HEAT binding was significantly shifted to the right after 2 h hypoxia.CONCLUSIONS:
Prolonged hypoxia in neonatal rat ventricular myocytes increases alpha 1 adrenoceptor density without change in antagonist affinity. Inositol phosphates follow a biphasic response, increasing after 1 h and decreasing after 2 h hypoxia in response to (-)-noradrenaline stimulation. This second messenger response and the rightward shift of the (-)-noradrenaline displacement curve suggests that after 2 h hypoxia there is a decrease in agonist affinity for the alpha 1 adrenoceptor consistent with uncoupling of the alpha 1 adrenoceptor from its effector.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Oxigênio
/
Transdução de Sinais
/
Receptores Adrenérgicos alfa
/
Animais Recém-Nascidos
/
Miocárdio
Limite:
Animals
Idioma:
En
Ano de publicação:
1991
Tipo de documento:
Article