Inhibition of voltage-gated Ca2+ current by PACAP in rat adrenal chromaffin cells

Mark S. Jorgensen, Jihong Liu, Julye M. Adams, William B. Titlow, Brian A. Jackson

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


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 Ca2+ 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 Ca2+ 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 Ca2+ transients and catecholamine secretion in rat chromaffin cells. Exposure to PACAP and PMA significantly reduced peak Ca2+ current in rat cells. The effects of both PACAP and PMA on Ca2+ 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 Ca2+ channels. PACAP pretreatment significantly reduced Ca2+ 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.

Original languageEnglish
Pages (from-to)59-65
Number of pages7
JournalRegulatory Peptides
Issue number1
StatePublished - Jan 15 2002

Bibliographical note

Funding Information:
The authors would like to thank Dr. Warwick Arden, Department of Cardiovascular Surgery, University of Kentucky, for the use of the Attofluor Fluorescence Imaging System. This research was supported by the National Institutes of Health (AG00873), the USDA (9602365), and by a predoctoral fellowship to JMA from the American Heart Association, Ohio Valley Affiliate.


  • Acetylcholine
  • Adrenal medulla
  • Catecholamines
  • Ion channels
  • Secretion
  • Signaling crosstalk

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Endocrinology
  • Clinical Biochemistry
  • Cellular and Molecular Neuroscience


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