Modulation of ACh-induced currents in rat adrenal chromaffin cells by ligands of α2 adrenergic and imidazoline receptors

The aim of this study was to investigate the expression of the α2-adrenergic 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-polymerase chain reaction (RT-PCR) performed on punches of rat adrenal medulla demonstrated expression of mRNA for the α2A-, α2B- and α2C-adrenergic receptors. Similar experiments conducted with tissue punches obtained from the adrenal cortex did not reveal expression of these receptor subtypes. Whole-cell currents were recorded in isolated chromaffin cells using the perforated-patch configuration. ACh (50 μM) evoked inward currents with a peak amplitude of 117.8±9.3 pA (n=45; Vhol=−60 mV). The currents were inhibited in a dose-dependent manner (0.5–50 μM) by clonidine, UK 14,304 and rilmenidine (agonists of α2/imidazoline receptors), as well as by SKF 86466 and efaroxan (antagonists). Adrenaline and noradrenaline (50–100 μM) had no significant effect. Thus, although the adrenal medulla expresses mRNA for the α2-adrenergic receptors, the lack of agonist–antagonist specificity observed in our whole-cell recordings (in the absence of intracellular dialysis) provides additional evidence against the possibility that these inhibitory effects are mediated by classical α2 or imidazoline receptor interactions.