A PACAP-activated network for secretion requires coordination of Ca2+ influx and Ca2+ mobilization.
Mol Biol Cell
; 35(7): ar92, 2024 Jul 01.
Article
em En
| MEDLINE
| ID: mdl-38758660
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 (PLCε) 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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Cálcio
/
Células Cromafins
/
Sinalização do Cálcio
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Retículo Endoplasmático
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Polipeptídeo Hipofisário Ativador de Adenilato Ciclase
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Receptores de Inositol 1,4,5-Trifosfato
Limite:
Animals
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article