Pretreatment with N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline accelerates the electroshock-induced decrease in density of β-adrenoceptors but not functional downregulation

Abstract

Intrapritoneal injection of N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) to rats significantly reduced the density of α 1- and α 2-adrenoceptors in the cerebral cortex, without affecting β-adrenoceptors. A single dose of EEDQ markedly accelerated the development of downregulation of β-adrenoceptors induced by a short series of electroshocks. The accumulation of cAMP, induced by isoproterenol, was unchanged in rats treated with EEDQ, while the effect of noradrenaline was reduced, to the level observed after isoproterenol alone, indicating the attenuation of α-adrenoceptor function. The isoproterenol-induced accumulation of cAMP was not changed by EEDQ nor electroshock, not by the combined treatment. The stimulatory action of noradrenaline was reduced after EEDQ alone or in combination with electroshock, but the effect of electroshock alone was insignificant. The results suggest that the acceleration of downregulation of β-adrenoceptors after combined treatment with an α-adrenoceptor blocking agent is related to elimination of the α-adrenergic potentiation of accumulation of cAMP mediated by β-adrenoceptors.