{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Morales A"],"funding":["American Heart Association","NIDA NIH HHS","American Heart Association-American Stroke Association","NINDS NIH HHS","National Institutes of Health","NIGMS NIH HHS","NIH HHS"],"pagination":["e202213180"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9770323"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["155(2)"],"pubmed_abstract":["The adrenomedullary chromaffin cell transduces chemical messages into outputs that regulate end organ function throughout the periphery. At least two important neurotransmitters are released by innervating preganglionic neurons to stimulate exocytosis in the chromaffin cell-acetylcholine (ACh) and pituitary adenylate cyclase activating polypeptide (PACAP). Although PACAP is widely acknowledged as an important secretagogue in this system, the pathway coupling PACAP stimulation to chromaffin cell secretion is poorly understood. The goal of this study is to address this knowledge gap. Here, it is shown that PACAP activates a Gαs-coupled pathway that must signal through phospholipase C ε (PLCε) to drive Ca2+ entry and exocytosis. PACAP stimulation causes a complex pattern of Ca2+ signals in chromaffin cells, leading to a sustained secretory response that is kinetically distinct from the form stimulated by ACh. Exocytosis caused by PACAP is associated with slower release of peptide cargo than exocytosis stimulated by ACh. Importantly, only the secretory response to PACAP, not ACh, is eliminated in cells lacking PLCε expression. The data show that ACh and PACAP, acting through distinct signaling pathways, enable nuanced and variable secretory outputs from chromaffin cells."],"journal":["The Journal of general physiology"],"pubmed_title":["PACAP and acetylcholine cause distinct Ca2+ signals and secretory responses in chromaffin cells."],"pmcid":["PMC9770323"],"funding_grant_id":["R35 GM127303","R35GM127303","R37DA0333987","R01 GM111997","R37 DA039997","R01GM111997/NS122534","17GRNT33661156","R01 NS122534"],"pubmed_authors":["Currie KPM","Smrcka AV","Kammermeier PJ","Axelrod D","Anantharam A","Bendahmane M","Watch L","Morales A","Traynor JR","West JL","Mohan R","Giovannucci DR","Chen X","Coffman BL","Bakshi S"],"additional_accession":[]},"is_claimable":false,"name":"PACAP and acetylcholine cause distinct Ca2+ signals and secretory responses in chromaffin cells.","description":"The adrenomedullary chromaffin cell transduces chemical messages into outputs that regulate end organ function throughout the periphery. At least two important neurotransmitters are released by innervating preganglionic neurons to stimulate exocytosis in the chromaffin cell-acetylcholine (ACh) and pituitary adenylate cyclase activating polypeptide (PACAP). Although PACAP is widely acknowledged as an important secretagogue in this system, the pathway coupling PACAP stimulation to chromaffin cell secretion is poorly understood. The goal of this study is to address this knowledge gap. Here, it is shown that PACAP activates a Gαs-coupled pathway that must signal through phospholipase C ε (PLCε) to drive Ca2+ entry and exocytosis. PACAP stimulation causes a complex pattern of Ca2+ signals in chromaffin cells, leading to a sustained secretory response that is kinetically distinct from the form stimulated by ACh. Exocytosis caused by PACAP is associated with slower release of peptide cargo than exocytosis stimulated by ACh. Importantly, only the secretory response to PACAP, not ACh, is eliminated in cells lacking PLCε expression. The data show that ACh and PACAP, acting through distinct signaling pathways, enable nuanced and variable secretory outputs from chromaffin cells.","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Feb","modification":"2025-04-22T01:56:53.097Z","creation":"2025-04-05T20:13:36.453Z"},"accession":"S-EPMC9770323","cross_references":{"pubmed":["36538657"],"doi":["10.1085/jgp.202213180"]}}