title: Modulation of ACh-induced currents in rat adrenal chromaffin cells by ligands of alpha2 adrenergic and imidazoline receptors.
abstract: The aim of this study was to investigate the expression of the alpha2-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 2A-, alpha2B- and alpha2C-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 microM) 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 microM) by clonidine, UK 14,304 and rilmenidine (agonists of alpha2/imidazoline receptors), as well as by SKF 86466 and efaroxan (antagonists). Adrenaline and noradrenaline (50-100 microM) had no significant effect. Thus, although the adrenal medulla expresses mRNA for the alpha2-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 alpha2 or imidazoline receptor interactions.
authors.affiliation: Department of Physiology, Faculty of Medicine and Health Science, University of Auckland, New Zealand.
authors.forename: M
authors.initials: M
authors.lastname: Takeda
authors.forename: J K
authors.initials: JK
authors.lastname: Phillips
authors.forename: R
authors.initials: R
authors.lastname: Dubey
authors.forename: J W
authors.initials: JW
authors.lastname: Polson
authors.forename: J
authors.initials: J
authors.lastname: Lipski
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology*; D000311:Adrenal Glands / Q000187:drug effects / Q000502:physiology*; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D002395:Catecholamines / Q000096:biosynthesis; D019439:Chromaffin Cells / Q000187:drug effects / Q000502:physiology*; D004553:Electric Conductivity; D004594:Electrophysiology; D004798:Enzymes / Q000235:genetics / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D054755:Imidazoline Receptors; D008024:Ligands; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D011942:Receptors, Adrenergic, alpha / Q000235:genetics / Q000502:physiology*; D011955:Receptors, Drug / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*
chemical_list: D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D002395:Catecholamines; D004798:Enzymes; D054755:Imidazoline Receptors; D008024:Ligands; D011942:Receptors, Adrenergic, alpha; D011955:Receptors, Drug; D000109:Acetylcholine