The Hop Cassette of the PAC1 Receptor Confers Coupling to Ca2+ Elevation Required for Pituitary Adenylate Cyclase-activating Polypeptide-evoked Neurosecretion

Mustafa, Tomris; Grimaldi, M.; Eiden, Lee E.

doi:10.1074/jbc.m609638200

Cited by 44 publications

(67 citation statements)

References 67 publications

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“…The very short PAC1 receptor is characterized by a 21-amino-acid deletion in the N-terminal extracellular domain, and PAC1R TM4 differs from the short variant by discrete sequences in transmembrane domains II and IV. Different splice variants are expressed during the development and differentiation of the nervous system (Zhou et al 2000), and the pathway regulated by PAC1 receptors is different in distinct cell types depending on the expressed splice variant, the PACAP concentration, and other factors present (Alexandre et al 2002;Chatterjee et al 1996;Daniel et al 2001;Lelievre et al 2002;Lutz et al 2006;Lyu et al 2000;Mustafa et al 2007;Nicot and DiCicco-Bloom 2001;Pantaloni et al 1996;Pisegna and Wank 1996).…”

Section: Discussionmentioning

confidence: 99%

Agonistic Behavior of PACAP6-38 on Sensory Nerve Terminals and Cytotrophoblast Cells

et al. 2008

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The effects of pituitary adenylate cyclase activating polypeptide (PACAP) are mediated through G-protein-coupled receptors, the specific PAC1 receptor and VPAC1 and VPAC2 receptors which bind vasoactive intestinal peptide with similar affinity. Based on binding affinity studies, PACAP6-38 was discovered as a potent antagonist of PAC1 and it has been used by hundreds of studies as a PACAP antagonist. Recently, we have found that in certain cells/tissues, PACAP6-38 does not antagonize PACAP-induced effects, but surprisingly, it exerts similar actions to PACAP1-38, behaving as an agonist. In the present study, we report on the agonistic behavior of PACAP6-38 on neuropeptide release from sensory nerves of the isolated rat trachea and on the MAPK signaling pathways in cytotrophoblast cells. In isolated rat tracheae, PACAP6-38, similarly to PACAP1-38, induced significant inhibitory effects on the release of three simultaneously measured sensory neuropeptides, substance P, calcitonin gene-related peptide, and somatostatin evoked by both chemical excitation and electrical field stimulation of capsaicin-sensitive afferents. Effects of PACAP6-38 were the same as those of PACAP1-38 on MAPK signaling in human cytotrophoblast cells. Western blot analysis showed that both peptide forms stimulated ERK1/2 and JNK phosphorylation, while they both inhibited p38 MAPK phosphorylation. The most pronounced effects were observed when both peptides were present. In summary, our results show that PACAP6-38, which is a PACAP receptor antagonist in most cells/tissues, can behave as an agonist in other systems. The increasing interest in the effects of PACAP requires further studies on the pharmacological properties of the peptide and its analogues.

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Section: Discussionmentioning

confidence: 99%

Agonistic Behavior of PACAP6-38 on Sensory Nerve Terminals and Cytotrophoblast Cells

et al. 2008

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“…during adipogenesis [85] or in osteoblast cells [84], furthermore CREB phosphorylation is regulated by the MAPK system in MC3T3 cells [86]. Additionally, intracellular Ca 2+ concentration can be elevated by PACAP [87] or VIP [88], resulting in an activation of classical PKCs and ERK both influencing osteoblast differentiation [89]. Nonetheless, PACAP treatment of UMR-106 cells did not alter the Ca 2+ concentration of these osteoblast cells, and activation of classical PKCs was not detected, in our experiments [16] (Fig.…”

Section: Vip and Pacap In Osteogenic Signaling Cascadesmentioning

confidence: 99%

PACAP and VIP signaling in chondrogenesis and osteogenesis

et al. 2015

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“…Exogenous PACAP evokes catecholamine secretion from chromaffin cells through a rapid influx of extracellular Ca 2+ (O'Farrell and Marley 1997; Tanaka et al 1996). PACAP-mediated exocytosis is independent of nicotinic ACh receptor (nAChR) function (Morita et al 2002; Watanabe et al 1992) or sodium-based action potentials (Mustafa et al 2007). Thus, synaptic PACAP signaling bypasses the key sites of depolarization-initiated release that are triggered by nicotinic receptor stimulation, and linked to pronounced secretory desensitization.…”

Section: Dual Transmission — Early Evidence and Implication Of Peptidmentioning

confidence: 99%

Is PACAP the Major Neurotransmitter for Stress Transduction at the Adrenomedullary Synapse?

Smith

Eiden

2012

J Mol Neurosci

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It has been known for more than a decade that the neuropeptide PACAP (pituitary adenylate cyclase-activating polypeptide) is co-stored with acetylcholine in the splanchnic nerve terminals innervating the adrenal medulla. Both transmitters are robust secretagogues for catecholamine release from chromaffin cells. Here, we review the unique contribution of PACAP to the functioning of the splanchnic–adrenal synapse in stress. While acetylcholine is released across a wide range of firing frequencies, PACAP is released only at high frequencies of stimulation, and its role in the regulation of epinephrine secretion and biosynthesis is highly specialized. PACAP is responsible for long-term catecholamine secretion using secretory mechanisms different from the rapidly desensitizing depolarization evoked by acetylcholine through nicotinic receptor activation. PACAP signaling also maintains catecholamine synthesis required for sustained secretion during prolonged stress via induction of the enzymes TH and PNMT, and enhances transcription of additional secreted molecules found in chromaffin cells that alter further secretion through both autocrine and paracrine mechanisms. PACAP thus mediates chromaffin cell plasticity via functional encoding of cellular experience. These features of PACAP action at the splanchnic–adrenal synapse may be paradigmatic for the general actions of neuropeptides as effectors of stimulus–secretion–synthesis coupling in stress.

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The Hop Cassette of the PAC1 Receptor Confers Coupling to Ca2+ Elevation Required for Pituitary Adenylate Cyclase-activating Polypeptide-evoked Neurosecretion

Cited by 44 publications

References 67 publications

Agonistic Behavior of PACAP6-38 on Sensory Nerve Terminals and Cytotrophoblast Cells

Agonistic Behavior of PACAP6-38 on Sensory Nerve Terminals and Cytotrophoblast Cells

PACAP and VIP signaling in chondrogenesis and osteogenesis

Is PACAP the Major Neurotransmitter for Stress Transduction at the Adrenomedullary Synapse?

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