title: Inhibition of voltage-gated Ca(2+) current by PACAP in rat adrenal chromaffin cells.
abstract: It is well established that pituitary adenylate cyclase-activating polypeptide (PACAP) can stimulate catecholamine biosynthesis and secretion in adrenal chromaffin cells. Recent studies from this laboratory demonstrated that PACAP pretreatment inhibits nicotine (NIC)-induced intracellular Ca(2+) transients and catecholamine secretion in porcine adrenal chromaffin cells. Mechanistically, this effect is mediated by protein kinase C (PKC), and based on indirect evidence, is thought to primarily target voltage-gated Ca(2+) channels. The present study used whole-cell patch-clamp analysis to test this possibility more directly in rat chromaffin cells. Consistent with the porcine data, pretreatment with PACAP or with phorbol ester [phorbol myristate acetate (PMA)] significantly suppressed NIC-induced intracellular Ca(2+) transients and catecholamine secretion in rat chromaffin cells. Exposure to PACAP and PMA significantly reduced peak Ca(2+) current in rat cells. The effects of both PACAP and PMA on Ca(2+) current could be blocked by treating cells with the PKC inhibitor staurosporine. Exposure to selective channel blockers demonstrated that rat chromaffin cells contain L-, N- and P/Q-type Ca(2+) channels. PACAP pretreatment significantly reduced Ca(2+) current gated through all three channel subtypes. These data suggest that PACAP can negatively modulate NIC-induced catecholamine secretion in both porcine and rat adrenal chromaffin cells.
authors.affiliation: Department of Physiology, College of Medicine, University of Kentucky, Lexington, KY 40536-0298, USA.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Jorgensen
authors.forename: Jihong
authors.initials: J
authors.lastname: Liu
authors.forename: Julye M
authors.initials: JM
authors.lastname: Adams
authors.forename: William B
authors.initials: WB
authors.lastname: Titlow
authors.forename: Brian A
authors.initials: BA
authors.lastname: Jackson
mesh_terms: D000313:Adrenal Medulla / Q000166:cytology / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000502:physiology*; D002395:Catecholamines / Q000378:metabolism; D019439:Chromaffin Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D003600:Cytosol / Q000737:chemistry; D004553:Electric Conductivity; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000502:physiology; D008297:Male; D009479:Neuropeptides / Q000494:pharmacology*; D009538:Nicotine / Q000037:antagonists & inhibitors; D018408:Patch-Clamp Techniques; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D051381:Rats; D017207:Rats, Sprague-Dawley; D019311:Staurosporine / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: C495403:Adcyap1 protein, rat; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D002395:Catecholamines; D009479:Neuropeptides; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D009538:Nicotine; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium