cAMP-dependent down-regulation of endothelin-1 receptors on rat astrocytoma C6 cells

Abstract The density of endothelin-1 (ET-1) receptors on rat astrocytoma C6 cells is down-regulated by activation of protein kinase C (PKC) [6]. We have investigated whether intracellular accumulation of cyclic adenosine monophosphate (cAMP) may also modulate surface ET-1 receptor number. The density of ET-1 receptors was measured by binding of [ 125 I]ET-1 on rat astrocytoma C6 intact cells exposed to catecholamines, dibutyryl-cAMP or forskolin. Prolonged exposure of the cells to the β-adrenergic agonists, isoproterenol or noradrenaline, results in a time- and dose-dependent decrease in cell surface ET-1 receptor number. This decrease proceeds slowly: maximal down-regulation is obtained by 6–7 h and sustained for up to 24 h in the presence of 10 μM isoproterenol. Since this down-regulation is mimicked by dibutyryl-cAMP (4 μM) and by forskolin (10 μM), we conclude that ET-1 receptors are susceptible to down-regulation through a cAMP-dependent pathway.