Modulation of ACh-induced currents in rat adrenal chromaffin cells by ligands of alpha(2) adrenergic and imidazoline receptors

The aim of this study was to investigate the expression of the alpha (2)-ad renergic receptors in the adrenal medulla, and to examine the mechanism by which clonidine and related drugs inhibit acetylcholine (ACh)-induced whole -cell currents in adrenal chromaffin cells. Reverse transcription-polymeras e chain reaction (RT-PCR) performed on punches of rat adrenal medulla demon strated expression of mRNA for the alpha (2A)-, alpha (2B-) and alpha (2C)- adrenergic receptors. Similar experiments conducted with tissue punches obt ained from the adrenal cortex did not reveal expression of these receptor s ubtypes. Whole-cell currents were recorded in isolated chromaffin cells usi ng the perforated-patch configuration. ACh (50 muM) evoked inward currents with a peak amplitude of 117.8 +/- 9.3 pA (n = 45; V-hol = -60 mV). The cur rents were inhibited in a dose-dependent manner (0.5-50 muM) by clonidine, UK 14,304 and rilmenidine (agonists of alpha (2)/imidazoline receptors), as well as by SKF 86466 and efaroxan (antagonists). Adrenaline and noradrenal ine (50-100 muM) had no significant effect. Thus, although the adrenal medu lla expresses mRNA for the alpha (2)-adrenergic receptors, the lack of agon ist-antagonist specificity observed in our whole-cell recordings (in the ab sence of intracellular dialysis) provides additional evidence against the p ossibility that these inhibitory effects are mediated by classical alpha (2 ) or imidazoline receptor interactions. (C) 2001 Elsevier Science B.V. All rights reserved.