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Phospholipase C-e defines a PACAP-stimulated pathway for secretion in the chromaffin cell
Journal article   Open access   Peer reviewed

Phospholipase C-e defines a PACAP-stimulated pathway for secretion in the chromaffin cell

Xiaohuan Chen, Breanna L. Coffman, Rebecca L. Brindley, Jason D Galpin, Christopher A Ahern, Kevin P. M. Currie, Alan V Smrcka, Daniel Axelrod and Arun Anantharam
Journal of neuroendocrinology, Vol.35(11), e13255
11/2023
DOI: 10.1111/jne.13255
PMCID: PMC10790106
PMID: 36970756
url
https://doi.org/10.1111/jne.13255View
Published (Version of record) Open Access

Abstract

Adrenomedullary chromaffin cells respond to splanchnic (sympathetic) nerve stimulation by releasing stress hormones into the circulation. The signal for hormone secretion is encoded in the neurotransmitters - especially acetylcholine (ACh) and pituitary adenylate cyclase activating polypeptide (PACAP) - that are released into the splanchnic-chromaffin cell synapse. However, functional differences in the effects of ACh and PACAP on the chromaffin cell secretory response are not well defined. Here, selective agonists of PACAP receptors or nicotinic and muscarinic acetylcholine receptors were applied to chromaffin cells. The major differences in the effects of these agents were not on exocytosis, per se, but rather on the steps upstream of exocytosis. In almost every respect, the properties of individual fusion events triggered by PACAP and cholinergic agonists were similar. On the other hand, the properties of the Ca2+ transients evoked by PACAP differed in several ways from those evoked by muscarinic and nicotinic receptor stimulation. A defining feature of the PACAP-stimulated secretory pathway was its dependence on signaling through exchange protein directly activated by cAMP (Epac) and PLCe. However, the absence of PLCe did not disrupt Ca2+ transients evoked by cholinergic agonists. Accordingly, inhibition of Epac activity did not disrupt secretion triggered by acetylcholine or specific agonists of muscarinic and nicotinic receptors. Thus, PACAP and acetylcholine stimulate chromaffin cell secretion via separate and independent pathways. This feature of stimulus-secretion coupling may be important for sustaining hormone release from the adrenal medulla under conditions associated with the sympathetic stress response.
Endocrinology & Metabolism Life Sciences & Biomedicine Neurosciences Neurosciences & Neurology Science & Technology

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