Regulation of chromogranin A transcription and catecholamine secretion by the neuropeptide PACAP. Stimulation and desensitization.

Abstract

We propose a model depicting putative signal transduction pathways underlying PACAP-induced CGA transcription and catecholamine secretion in PC12 cells (Fig 7). PACAP mediates both secretion and transcription through the PAC 1 receptor, but with quite different post-receptor signaling pathways. PACAP signals to CGA transcription through a Ca2+-independent pathway involving the CGA promoter CRE domain in cis and PKA and the transcription factor CREB in trans. PACAP-evoked secretion and transcription are subject to homologous desensitization in PC 12 cells; however, PACAP also provokes long-lasting secretion, even under dose and time circumstances where acute, DHP-sensitive secretion has been desensitized. While initial secretion is mediated by an L-type VOCC, extended secretion may involve a SOCC activated through a Gq/11/PLC-β/PI signaling pathway. Further characterization of PACAP signaling pathways will require definitive identification of the SOCC channel involved in the sustained catecholamine release.