Abbreviations used : CsA, cyclosporin A ; IP3, inositol trisphosphate ; PACAP, pituitary adenylate cyclase-activating polypeptide ; VIP, vasoactive intestinal polypeptide.
Pituitary Adenylate Cyclase-Activating Polypeptide Regulation of Vasoactive Intestinal Polypeptide Transcription Requires Ca2+ Influx and Activation of the Serine/Threonine Phosphatase Calcineurin
Article first published online: 13 JUN 2002
Journal of Neurochemistry
Volume 73, Issue 4, pages 1769–1772, October 1999
How to Cite
Lee, H.-W., Hahm, S. H., Hsu, C.-M. and Eiden, L. E. (1999), Pituitary Adenylate Cyclase-Activating Polypeptide Regulation of Vasoactive Intestinal Polypeptide Transcription Requires Ca2+ Influx and Activation of the Serine/Threonine Phosphatase Calcineurin. Journal of Neurochemistry, 73: 1769–1772. doi: 10.1046/j.1471-4159.1999.731769.x
- Issue published online: 13 JUN 2002
- Article first published online: 13 JUN 2002
- Vasoactive intestinal polypeptide;
- Primary chromaffin cells;
- Pituitary adenylate cyclase-ac-tivating polypeptide;
- Calcium influx;
- Calcineurin activation
Abstract : A > 15-fold increase in vasoactive intestinal polypeptide (VIP) mRNA and VIP peptide levels occurred in primary chromaffin cells following exposure to the neurotrophic neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP)-27 with an EC50 of ~2 nM. PACAP induction of VIP expression was blocked by methoxyverapamil or by a combination of nimodipine and ω-conotoxin MVIIC, indicating a requirement for PACAP-initiated calcium entry through voltage-dependent calcium channels for regulation of VIP biosynthesis. Ascomycin, which inhibits calcineurin through formation of an ascomycin/FKBP12/calcineurin ternary complex, abolished the PACAP-evoked increase in VIP expression, whereas rapamycin, which also binds to FKBP12 but does not cause inhibition of calcineurin, did not. Cyclosporin A, which inhibits calcineurin through formation of a cyclosporin A/cyclophilin/calcineurin complex, also abolished PACAP-evoked VIP biosynthesis. These data indicate that PACAP regulates the expression of VIP via a signaling pathway that requires calcium influx and activation of calcineurin.