A novel neuropeptide, pituitary adenylate cyclase-activating polypeptide (PACAP), in human intestine: evidence for reduced content in Hirschsprung's disease

Abstract

A novel neuropeptide, pituitary adenylate cyclase-activating polypeptide (PACAP), exhibits sequence homology with vasoactive intestinal polypeptide (VIP) and occurs in the mammalian brain, lung and gut. The distribution of PACAP in ganglionic and aganglionic portions of the large intestine of patients with Hirschsprung's disease was examined by immunohistochemistry and radioimmunoassay. PACAP-immunoreactive nerve fibers were distributed in all layers of the ganglionic and aganglionic segments of the intestine, although they were less numerous in the latter, and PACAP-immunoreactive nerve cell bodies were seen in the ganglionic portion of the intestine. The concentration of immunoreactive PACAP was lower in the aganglionic than in the ganglionic segment of the intestinal wall. PACAP and VIP were found to coexist in both ganglionic and aganglionic segments of the intestine. Apparently, PACAP participates in the regulation of gut motility. The scarcer PACAP innervation of the aganglionic segment may contribute to the defect in intestinal relaxation seen in patients with Hirschsprung's disease.

Pituitary Adenylate Cyclase-Activating Polypeptide and Its Receptors: 20 Years after the Discovery

“…The presence of PACAP-immunoreactive cell bodies has been observed in the myenteric ganglia throughout the gastrointestinal tract, and the existence of intrinsic neurons has been confirmed by in situ hybridization (Shen et al, 1992;Hannibal et al, 1998). Numerous PACAP-containing nerve fibers have been visualized along the circular muscle fibers and in the longitudinal smooth muscle layer of the esophagus (Uddman et al, 1991a;Köves et al, 1993;Olsson and Holmgren, 1994).…”

Localization and characterization of neuropeptide receptors in human colon

“…Neurotransmission is mediated not only by the "classical" neurotransmitters but also by neuropeptide transmitters like somatostatin (SRIF), substance P (SP), neurotensin, gastrin, cholecystokinin (CCK), neuropeptide Y (NPY), gastrin-releasing peptide (GRP), vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating peptide (PACAP) (Furness et al 1992;McConalogue and Furness 1994;Schultzberg et al 1980). These neuropeptides have been identified with immunohistochemical methods in the enteric nervous system in rats and guinea-pigs (Ekblad et al 1988;Hökfelt et al 2001;Larsson and Sundler 1990;Shen et al 1992), and shown to interact with many specific targets like the smooth muscles, the vessels, the mucosa and the lymphoid tissues. They act on the regulation of gut motility, blood flow, secretion and nutrient absorption as well as on the modulation of the immune response (McConalogue and Furness 1994).…”

Cloning and Characterization of the Signal Transduction of Four Splice Variants of the Human Pituitary Adenylate Cyclase Activating Polypeptide Receptor

“…PACAP has been shown to exhibit a protective role against the neuronal toxicity of the gp120 envelope protein of the human immunodeficiency virus suggesting its role as a neurotrophic factor (8). In the human gastrointestinal tract, PACAP may modulate smooth muscle motility as evidenced by a reduction in immunoreactive PACAP nerve fibers in Hirshsprung's disease (9). Type 1 PACAP receptors have also been described on the human lung carcinoma cell lines NCI-H345 and NCI-N417 and the human neuroblastoma cell line NB-OK-1, where they stimulate clonal growth (10,11).…”