Loss of beta-adrenoceptor response in myocytes overexpressing the Na+/Ca(2+)-exchanger.

Article Details

Citation

Copy to clipboard

Sato M, Gong H, Terracciano CM, Ranu H, Harding SE

Loss of beta-adrenoceptor response in myocytes overexpressing the Na+/Ca(2+)-exchanger.

J Mol Cell Cardiol. 2004 Jan;36(1):43-8.

PubMed ID

14734046 [ View in PubMed

]

Abstract

Increased Na+/Ca(2+)-exchanger (NCX) and altered beta-adrenoceptor (betaAR) responses are observed in failing human heart. To determine the possible interaction between these changes, we investigated the effect of NCX overexpression on responses to isoproterenol in adult rat ventricular myocytes. Responses to isoproterenol were largely mediated through the beta1AR in control myocytes. Adenovirally-mediated overexpression of NCX, at levels, which did not alter basal contraction of myocytes, markedly depressed the isoproterenol concentration-response curve. Responses to isoproterenol could be restored to normal by beta2AR blockade, suggesting a beta2AR-mediated inhibition of beta1AR signalling. Pertussis toxin normalised isoproterenol responses in NCX cells, indicating that beta2AR effects were mediated by Gi. Negative-inotropic effects of high concentrations of ICI 118,551, previously shown to be due to beta2AR-Gi coupling, were increased in NCX cells. We conclude that NCX upregulation can markedly alter the consequences of betaAR stimulation and that this may contribute to the alterations in betaAR response seen in failing human heart.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Isoprenaline	Beta-1 adrenergic receptor	Protein	Humans	Yes	Agonist	Details