Effect of dexmedetomidine on the release of [ 3H]-noradrenaline from rat kidney cortex slices: characterization of α 2-adrenoceptor

Abstract

The presynaptic modulation of [ 3H]-noradrenaline (NA) release from rat kidney cortex slices, a method used for the first time, was investigated. Rat kidney cortex slices were loaded with [ 3H]-NA and the release of radioactivity at rest and in response to field stimulation was determined. The α 2-adrenoceptor agonist, dexmedetomidine inhibited the stimulation-evoked release of NA from kidney slices in a concentration-dependent manner, whereas α 2-adrenoceptor antagonist CH-38083 (7,8-methyenedioxy-14-alpha-hydroxyalloberbane HCl), an α 2-adrenoceptor antagonists, enhanced it. When dexmedetomidine and BRL-44408, a selective α 2A antagonist, were added together, the effect of dexmedetomidine was significantly antagonized. In contrast, ARC-239 (2-(2,4-( o-piperazine-1-yl)-ethyl-4,4-dimethyl-1,3-(2H, 4H)disoguinolinedione chloride), a selective α 2B-antagonist, had no effect on the release and failed to prevent the effect of dexmedetomidine. Prazosin, an α 1- and α 2B/C-adrenoceptor antagonist enhanced the release evoked by field stimulation. It is therefore suggested that there is a negative feedback modulation of NA release at the sympathetic innervation of kidney cortex, and dexmedetomidine, a clinically used anesthetic adjunct inhibits the release via activation of α 2C-adrenoceptors.