Pituitary Adenylate Cyclase‐Activating Polypeptide (PACAP) Regulation of Sympathetic Neuron Neuropeptide Y and Catecholamine Expression

Abstract

Two forms of pituitary adenylate cyclase-activating polypeptide (PACAP), the 38-and 27-amino-acid forms (PACAP38 and PACAP27, respectively), which share amino acid sequence homology with vasoactive intestinal peptide (VIP), were evaluated for their abilities to regulate sympathetic neuron catecholamine and neuropeptide Y (NPY) expression . PACAP38 and PACAP27 potently and efficaciously stimulated NPY and catecholamine secretion in primary cultured superior cervical ganglion (SCG) neurons; 100-to 1,000-fold higher concentrations of VIP were required to modulate secretion, suggesting that SCG neurons express the PACAP-selective type I receptor . PACAP38 elicited a sustained seven-to ninefold increase in the rate of NPY secretion and threefold stimulation in the rate of catecholamine release. PACAP38 and PACAP27 produced parallel neuronal NPY and catecholamine release, but cellular levels of NPY and catecholamines were differentially regulated. Sympathetic neuron NPY content was decreased, whereas cellular total catecholamine levels were elevated by the PACAP peptides ; total NPY and catecholamine levels (secreted plus cellular content) were increased. In concert with the increased total peptide and transmitter production, pro-NPY and tyrosine hydroxylase mRNA levels were elevated . Furthermore, PACAP38 was more efficacious than PACAP27 in regulating pro-NPY and tyrosine hydroxylase mRNA . SCG neuronal expression of mRNA encoding the type I PACAP receptor further supported the studies demonstrating that sympathetic neuronal levels of NPY and catecholamine content and secretion and mRNA are differentially regulated by the PACAP peptides . Key Words: Pituitary adenylate cyclase-activating polypeptide-Vasoactive intestinal peptide-Superior cervical ganglion-Cell culture-Neuropeptide-Tyrosine hydroxylase. J. Neurochem. 65,978-987 (1995) .Pituitary adenylate cyclase-activating polypeptides (PACAPs) belong to the vasoactive intestinal peptide (VIP)/ secretin/glucagon family of bioactive peptides and mediate various physiological functions in neuroendocrine tissues . Isolated originally from ovine hypo-

Pituitary Adenylate Cyclase Activating Polypeptide in Stress-Related Disorders: Data Convergence from Animal and Human Studies

“…In addition, PACAP is found in preganglionic sympathetic neurons in the intermediolateral cell column of the thoracolumbar spinal cord and accordingly, PACAPergic fibers densely innervate sympathetic ganglia. Postganglionic sympathetic neurons selectively express PAC1 receptors at high levels and PACAP potently stimulates sympathetic NPY and catecholamine release, which has implicated PACAP peptides as one of the noncholinergic regulators of sympathetic function (21, 35). Congruently, PACAP is colocalized with acetylcholine in abdominal preganglionic splanchnic nerve terminal terminals innervating the adrenal medulla for epinephrine release.…”

Pituitary Adenylate Cyclase-activating Polypeptide (PACAP)/PAC1HOP1 Receptor Activation Coordinates Multiple Neurotrophic Signaling Pathways

“…The PAC 1 HOP1 receptor, by contrast, is dually coupled to Gα s and Gα q/11 to potently and efficaciously stimulate adenylate cyclase, phospholipase C, mitogen-activated protein kinase (MAPK), and other intracellular effectors that in aggregate have the potential of generating diverse cellular response (2, 10–12). Recent studies, for example, have shown that the PAC 1 HOP receptor isoform coupling to phospholipase C for calcium mobilization and influx is essential for neurotransmitter/neuropeptide release (13, 14). PAC 1 HOP1 receptor overexpression in embryonic cortical neurons results in phospholipase C activation, PKC translocation, and cellular calcium flux to facilitate proliferation (9, 15).…”

“…To examine the abilities for PACAP/PAC 1 receptor signaling to engage and coordinate these events in one neuronal system, we have employed primary sympathetic neurons that we have shown previously to preferentially express the PAC 1 HOP1 receptor isoform (13, 37, 38). All of the highly conserved members of the MAPK family, including ERK1 and ERK2 (p44 and p42, respectively), ERK5, JNK, and p38 MAPK, have been well described to participate in neuronal development, differentiation, cell cycle progression, and survival; how PAC 1 HOP1 receptor signaling impacts one or all of the MAPKs is not known.…”

Expression of pituitary adenylate cyclase-activating polypeptide (PACAP) and the PACAP-selective receptor in cultured rat astrocytes, human brain tumors, and in response to acute intracranial injury

“…PACAP is expressed throughout the central and peripheral nervous systems, where it exerts effects on neurite outgrowth (Deutsch et al 1993), neuropeptide and neurotransmitter production (May and Braas 1995), and neuronal proliferation (Lu and DiCicco-Bloom 1997;Villalba et al 1997). The diverse activities of PACAP are mediated by multiple-target tissue receptors.…”