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

The presynaptic modulation of [H-3]-noradrenaline (NA) release from rat kid ney cortex slices, a method used for the first time, was investigated. Rat kidney cortex slices were loaded with [H-3]-NA and the release of radioacti vity at rest and in response to field stimulation was determined. The alpha (2)-adrenoceptor agonist, dexmedetomidine inhibited the stimulation-evoked release of NA from kidney slices in a concentration-dependent manner, wher eas alpha (2)-adrenoceptor antagonist CH-38083 (7,8-methyenedioxy-14-alpha- hydroxyalloberbane HCl), an alpha (2)-adrenoceptor antagonists, enhanced it . When dexmedetomidine and BRL-44408, a selective alpha (2A) antagonist, we re added together, the effect of dexmedetomidine was significantly antagoni zed. In contrast, ARC-239 (2-(2,4-(o-piperazine-1- yl)-ethyl-4,4-dimethyl-1 ,3-(2H, 4H)disoguinolinedione chloride), a selective alpha (2B)-antagonist, had no effect on the release and failed to prevent the effect of dexmedeto midine. Prazosin, an alpha (1)- and alpha (2B/C)-adrenoceptor antagonist en hanced the release evoked by field stimulation. It is therefore suggested t hat there is a negative feedback modulation of NA release at the sympatheti c innervation of kidney cortex, and dexmedetomidine, a clinically used anes thetic adjunct inhibits the release via activation of alpha (2C)-adrenocept ors. (C) 2001 Elsevier Science Ltd. All rights reserved.