{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Chen X"],"funding":["NIDCR NIH HHS","NIMH NIH HHS","NINDS NIH HHS","NIGMS NIH HHS"],"pagination":["ar92"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11244167"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["35(7)"],"pubmed_abstract":["Chromaffin cells of the adrenal medulla transduce sympathetic nerve activity into stress hormone secretion. The two neurotransmitters principally responsible for coupling cell stimulation to secretion are acetylcholine and pituitary adenylate activating polypeptide (PACAP). In contrast to acetylcholine, PACAP evokes a persistent secretory response from chromaffin cells. However, the mechanisms by which PACAP acts are poorly understood. Here, it is shown that PACAP induces sustained increases in cytosolic Ca2+ which are disrupted when Ca2+ influx through L-type channels is blocked or internal Ca2+ stores are depleted. PACAP liberates stored Ca2+ via inositol trisphosphate receptors (IP3Rs) on the endoplasmic reticulum (ER), thereby functionally coupling Ca2+ mobilization to Ca2+ influx and supporting Ca2+-induced Ca2+-release. These Ca2+ influx and mobilization pathways are unified by an absolute dependence on phospholipase C epsilon (PLCĪµ) activity. Thus, the persistent secretory response that is a defining feature of PACAP activity, in situ, is regulated by a signaling network that promotes sustained elevations in intracellular Ca2+ through multiple pathways."],"journal":["Molecular biology of the cell"],"pubmed_title":["A PACAP-activated network for secretion requires coordination of Ca2+ influx and Ca2+ mobilization."],"pmcid":["PMC11244167"],"funding_grant_id":["R35 GM127303","R01 DE019245","T32 GM144873","R01 MH125849","R01 GM136826","R01 NS122534","R21 NS126779"],"pubmed_authors":["Yule DI","Smrcka AV","Kammermeier PJ","Axelrod D","Rabino AA","Bell NA","Giovannucci DR","Anantharam A","Chen X","Coffman BL","Garcia-Mata R"],"additional_accession":[]},"is_claimable":false,"name":"A PACAP-activated network for secretion requires coordination of Ca2+ influx and Ca2+ mobilization.","description":"Chromaffin cells of the adrenal medulla transduce sympathetic nerve activity into stress hormone secretion. The two neurotransmitters principally responsible for coupling cell stimulation to secretion are acetylcholine and pituitary adenylate activating polypeptide (PACAP). In contrast to acetylcholine, PACAP evokes a persistent secretory response from chromaffin cells. However, the mechanisms by which PACAP acts are poorly understood. Here, it is shown that PACAP induces sustained increases in cytosolic Ca2+ which are disrupted when Ca2+ influx through L-type channels is blocked or internal Ca2+ stores are depleted. PACAP liberates stored Ca2+ via inositol trisphosphate receptors (IP3Rs) on the endoplasmic reticulum (ER), thereby functionally coupling Ca2+ mobilization to Ca2+ influx and supporting Ca2+-induced Ca2+-release. These Ca2+ influx and mobilization pathways are unified by an absolute dependence on phospholipase C epsilon (PLCĪµ) activity. Thus, the persistent secretory response that is a defining feature of PACAP activity, in situ, is regulated by a signaling network that promotes sustained elevations in intracellular Ca2+ through multiple pathways.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Jul","modification":"2026-04-30T00:17:01.136Z","creation":"2025-04-04T08:18:06.438Z"},"accession":"S-EPMC11244167","cross_references":{"pubmed":["38758660"],"doi":["10.1091/mbc.E24-02-0083"]}}