Pituitary Adenylate Cyclase-activating Peptide (PACAP) Recruits Low Voltage-activated T-type Calcium Influx under Acute Sympathetic Stimulation in Mouse Adrenal Chromaffin Cells

Abstract

Background:The acute stress secretagogue PACAP leads to catecholamine release, but the source of calcium necessary for secretion is unknown. Results: PACAP stimulation increases LVA Ca v 3.2 influx in a PKC-dependent process. Conclusion: PACAP-mediated acute sympathetic stress functionally recruits a pool of latent Ca v 3.2 channels to supply calcium for secretion. Significance: Native sympathoadrenal stimulation elicits catecholamine release through a non-canonical mechanism.

Nickel suppresses the PACAP-induced increase in guinea pig cardiac neuron excitability

“…The PACAP peptide amino acid sequence is highly conserved, and the action of PACAP is tissue specific dependent on the activation of the different isoforms of the seven transmembrane G proteincoupled PACAP-selective PAC 1 receptor (Adcyap1r1) and/or the vasoactive intestinal peptide (VPAC) receptors (2,4,20,45,54). PACAP/PAC 1 receptor signaling modulates synaptic transmission and plasticity via pre-and postsynaptic mechanisms, and these effects have been shown to be critically important in central stress responses, peripheral sensory and autonomic function, and maintenance of physiological homeostasis (9,18,19,21,25,31,32,40,41,47,49,54).We previously identified colocalization of PACAP with acetylcholine in cholinergic parasympathetic preganglionic terminals innervating guinea pig cardiac neurons (5, 6) and demonstrated that both endogenously released and exogenously applied PACAP significantly increases cardiac neuron excitability through PAC 1 receptor activation (5,22,35,49). Cardiac neurons are more readily accessible than CNS neurons for experimental manipulations and accordingly, we have used these cells to further our understanding of cellular PAC 1 receptor signaling mechanisms.…”

“…The PACAP peptide amino acid sequence is highly conserved, and the action of PACAP is tissue specific dependent on the activation of the different isoforms of the seven transmembrane G proteincoupled PACAP-selective PAC 1 receptor (Adcyap1r1) and/or the vasoactive intestinal peptide (VPAC) receptors (2,4,20,45,54). PACAP/PAC 1 receptor signaling modulates synaptic transmission and plasticity via pre-and postsynaptic mechanisms, and these effects have been shown to be critically important in central stress responses, peripheral sensory and autonomic function, and maintenance of physiological homeostasis (9,18,19,21,25,31,32,40,41,47,49,54).…”

Expression and Role of T-type Calcium Channels during Neuroendocrine Differentiation

“…In mouse chromaffin cells in situ, short-term exposure to PACAP stimulates T-type calcium channel activity through a PKC-dependent recruitment of Cav3.2 channels to the plasma membrane [93]. Cav3.2 channels may therefore be responsible for catecholamine secretion in acute stress situations.…”

Functional upregulation of the H2S/Cav3.2 channel pathway accelerates secretory function in neuroendocrine-differentiated human prostate cancer cells

“…The enhanced activity of Ca v 3.2 by NaHS, a donor of H 2 S, also causes neuronal differentiation characterized by neurite outgrowth and functional upregulation of high voltage-activated Ca 2+ channels in NG108-15 cells (mouse neuroblastoma  rat glioma hybrid cells) [22][23][24]. Of interest is that Ca v 3.2 plays a role in low-threshold exocytosis in neurons or endocrine secretory cells [25][26][27] including neuroendocrine-like differentiated prostate cancer cells [28].…”