Summary
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.
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Cauvin A, Neef PD, Robberecht P, Gourlet P, Arimura A, Christophe J (1990) Properties and distribution of specific PACAP receptors in rat brain and medulla (abstract). Digestion 46 [Suppl]:16
Coons AH, Leduc EH, Conolly JM (1955) Studies of antibody production. I. A method for the histochemical demonstration of specific antibodies and its application to a study of the hyperimmune rabbit. J Exp Med 102:49–60
Costa M, Furness JB, Gibbins IL (1986) Chemical coding of enteric neurons. In: Hökfelt T, Fuxe K, Pernow B (eds) Coexistence of neuronal messengers: a new principle in chemical transmission. Prog Brain Res 68:217–239
Dupont C, Navarro J, Chenut B, Rosselin G (1980) Modifications of VIP intestinal content associated with abnormal nervous myenteric plexus: a biologic feature of chronic intestinal obstruction. J Pediatr 96:1037–1039
Gourler P, Woussen MC, Vandermeers A, Vandermeers-Piret MC, Robberecht P, Christophe J (1990) Pharmacological characterization of specific PACAP receptors in the rat pancreatic acinar cell line AR 4-2J (abstract). Digestion 46 [Suppl]:38
Hamada Y, Bishop AE, Federici G, Rivoseddhi M, Talbot IC, Polak JM (1987) Increased neuropeptide Y-immunoreactive innervation of aganglionic bowel in Hirschsprung's disease. Virchows Arch [A] 411:369–377
Ikawa H, Yokoyama J, Morikawa Y (1980) A quantitative study of acetylcholine in Hirschsprung's disease. J Pediatr Surg 15:48–52
Kamijio K, Hialt RB, Koelle GB (1953) Congenital megacolon. A comparison of the spastic and hypertrophied segments with the respect to cholinesterase activities and sensitivities to acethylcholine, DFP and the barium ion. Gastroenterology 24:173–185
Kimura C, Ohkubo S, Ogi K, Hosoya M, Itoh Y, Onda H, Miyata A, Jiang L, Dahl R, Stibbs HH, Arimura A, Fujino M (1990) A novel peptide which stimulates adenylate cyclase: molecular cloning and characterization of the ovine and human cDNAs. Biochem Biophys Res Commun 166:81–89
Köves K, Arimura A, Somogyvari-Vigh A, Vigh S, Miller J (1990) Immunohistochemical demonstration of a novel hypothalamic peptide, pituitary adenylate cyclase-activating polypeptide, in ovine hypothalamus. Endocrinology 127:264–271
Larsson LT, Sundler F (1990) Is the reduction of VIP the clue to the pathophysiology of Hirschsprung's disease? Z Kinderchir 45:164–166
Larsson LT, Malmfors G, Sundler F (1983) Peptidergic innervation in Hirschsprung's disease. Z Kinderchir 38:301–304
Larsson LT, Malmfors G, Wahlestedt C, Leander S, Håkanson R (1987) Hirschsprung's disease: a comparison of the nervous control of ganglionic and aganglionic smooth muscle in vitro. J Pediatr Surg 22:431–435
Larsson LT, Malmfors G, Sundler F (1988a) Neuropeptide Y (NPY), calcitonin gene-related peptide (CGRP) and galanin in Hirschsprung's disease. An immunocytochemical study. J Pediatr Surg 23:342–345
Larsson LT, Malmfors G, Sundler F (1988b) Defects in peptidergic innervation in Hirschsprung's disease. Pediatr Surg Int 3:147–155
Larsson LT, Malmfors G, Ekblad E, Ekman R, Sundler F (1991) NPY hyperinnervation in Hirschsprung's disease: both adrenergic and non-adrenergic fibers contribute. J Pediatr Surg 26:1207–12114
Luts A, Sundler F (1989) Peptide-containing nerve fibers in the respiratory tract of the ferret. Cell Tissue Res 258:259–267
Miyata A, Arimura A, Dahl RR, Minamino N, Uehara A, Jiang L, Culler MD, Coy DH (1989) Isolation of a novel 38 residue-hypothalamic polypeptide which stimulates adenylate cyclase in pituitary cells. Biochem Biophys Res Commun 164:567–574
Miyata A, Jang L, Dahl RR, Kitada C, Kubo K, Fujino M, Minamino N, Arimura A (1990) Isolation of neuropeptide corresponding to the N-terminal 27 residues of the pituitary adenylate cyclase activating polypeptide with 38 residues (PACAP 38). Biochem Biophys Res Commun 170:643–648
Mungan Z, Rossowski WJ, Ertan A, Coy DH, Arimura A (1991) Relaxant effect of pituitary adenylate cyclase activating polypeptide (PACAP) on rat intestinal smooth muscle (abstract). Gastroenterology 100:A474
Ogi K, Kimura C, Onda H, Arimura A, Fujino M (1990) Molecular cloning and characterization of cDNA for the precursor of rat pituitary adenylate cyclase activating peptide (PACAP). Biochem Biophys Res Commun 173:1271–1279
Schmidt WE, Höcker F, Katsoulis S, Gallwitz B, Stuber E, Schwarzhoff R, Schäfer F, Eckart K, Fölsch UR, Creutzfeldt W (1990) PACAP-27 and PACAP-38 synthesis and biological activity of two novel regulatory brain-gut peptides (abstract). Digestion 46 [Suppl]:101
Shen ZX, She YX, Wang WC, Wang LH (1990) Immunohistochemical study of peptidergic nerves in infantile hypertrophic pyloric stenosis. Pediatr Surg Int 5:110–113
Sundler F, Ekblad E, Håkanson R (1991) The neuroendocrine system of the gut — an update. Acta Oncologica 30:419–428
Sundler F, Ekblad E, Absood A, Håkanson R Köves K, Arimura A (1992) Pituitary adenylate cyclase activating peptides (PACAP), a novel VIP-like gut neuropeptide. Neuroscience 46:439–454
Swenson O, Rheinlander F, Diamond I (1949) Hirschsprung's disease: A new concept of the etiology. N Eng J Med 241:555–556
Taguchi T, Tanaka K, Ikeda K, Matsubayashi S, Yanaihara N (1983) Peptidergic innervation irregularities in Hirschsprung's disease-immunohistochemistry-radioimmunoassay. Virchows Arch [A] 401:223–235
Tam PKH (1986) An immunochemical study with neuron specific enolase and substance P of human enteric innervation — the normal developmental pattern and abnormal deviations in Hirschsprung's disease and pyloric stenosis. J Pediatr Surg 21:227–232
Tam PKH, Boyd GP (1990) Origin, course, and endings of abnormal enteric nerve fibres in Hirschsprung's disease defined by whole mount immunohistochemistry. J Pediatr Surg 25:457–461
Touloukian RJ, Aghajanian G, Roth RH (1973) Adrenergic hyper-activity of the aganglionic colon. J Pediatr Surg 8:191–195
Tsuto T, Okamura H, Fukui K, Obata HL, Terubayashi H, Iwai N, Majima S, Yanaihara N, Ibata Y (1982) An immunohistochemical investigation of vasoactive intestinal polypeptide in the colon of patients with Hirschsprung's disease. Neurosci Lett 34:57–62
Tsuto T, Okamura H, Fukui K, Tsuto HLO, Terubayashi H, Yanaihara J, Iwai N, Majima S, Yanaihara N, Ibata Y (1985) Immunohistochemical investigations of gut hormones in the colon of patients with Hirschsprung's disease. J Pediatr Surg 20:266–270
Uddman R, Luts A, Arimura A, Sundler F (1991) Pituitary adenylate cyclase-activating peptide (PACAP), a new vasoactive intestine peptide (VIP)-like peptide in the respiratory tract. Cell Tissue Res 265:197–201
Vizi ES, Zseli J, Kontor E, Feher E, Verebelyi T (1990) Characteristic of cholinergic neuroeffector transmission of ganglionic and aganglionic colon in Hirschsprung's disease. Gut 31:1046–1050
Weinberg AG (1970) The anorectal myenteric plexus: its relation to hypoganglionosis of the colon. Am J Clin Pathol 54:637–642
Wright PG, Sheperd JJ (1965) Response to drugs of isolated human colonic muscle from a case of Hirschsprung's disease. Lancet II:1161–1164
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Shen, Z., Larsson, L.T., Malmfors, G. et al. A novel neuropeptide, pituitary adenylate cyclase-activating polypeptide (PACAP), in human intestine: evidence for reduced content in Hirschsprung's disease. Cell Tissue Res 269, 369–374 (1992). https://doi.org/10.1007/BF00319630
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DOI: https://doi.org/10.1007/BF00319630