Pituitary adenylate cyclase activating peptide: A novel vasoactive intestinal peptide-like neuropeptide in the gut

doi:10.1016/0306-4522(92)90064-9

Neuroscience

Volume 46, Issue 2, January 1992, Pages 439-454

https://doi.org/10.1016/0306-4522(92)90064-9 Get rights and content

Abstract

Pituitary adenylate cyclase activating peptide (PACAP) is a vasoactive intestinal peptide (VIP)-like hypothalamic peptide occurring in two forms, PACAP-27 and the C-terminally extended PACAP-38. The predicted rat and human PACAP sequence is identical to the isolated ovine one. In the present study, the occurrence and distribution of PACAP-like peptides were examined in the gut of several species by immunocytochemistry and immunochemistry using an antibody raised against PACAP-27.

PACAP-like immunoreactivity was observed in nerve fibers in the gut wall of all species examined (chicken, mouse, rat, hamster, guinea-pig, ferret, cat, pig, sheep and man). In the chicken and human gut, immunoreactive fibers were numerous in all layers. In the other species examined the fibers were predominantly found in the myenteric ganglia and smooth muscle. Delicate PACAP-immunoreactive fibers were seen in the gastric mucosa of mouse, rat, hamster and man but not in the other species examined. The chicken proventriculus harbored numerous PACAP-immunoreactive endocrine cells which were identical with the serotonin-containing cells storing gastrin-releasing peptide.

PACAP-immunoreactive nerve cell bodies were numerous in the submucous ganglia and moderate in number in the myenteric ganglia of the human gut. They were few in the intramural ganglia of the other species examined. Extrinsic denervation (performed on segments of rat and guinea-pig small intestine) did not visibly affect the PACAP innervation, indicating an intramural origin of most PACAP-immunoreactive fibers. Double immunostaining for VIP and PACAP revealed co-existence of the two peptides in nerve cell bodies and nerve fibers of the human and chicken gut and in fibers in the gastric mucosa of mouse and rat. In all other species examined and in all other locations in the gut PACAP-immunoreactive nerve cell bodies and nerve fibers were distinct from those storing VIP; many of them contained gastrin-releasing peptide instead. Immunochemistry revealed PACAP-like peptides in gut extracts of all species studied; upon high performance liquid chromatography the immunoreactive material co-eluted with synthetic PACAP-27.

The distribution of PACAP-immunoreactive nerve cell bodies and nerve fibers in the gut wall suggests their involvement in the regulation of both motor and secretory activities.

References (20)

EkbladE. et al.
Projections of peptide-containing neurons in rat small intestine
Neuroscience
(1987)
HoshinoM. et al.
Primary structure of helodermin, a VIP-secretin-like peptide isolated from Gila monster venom
Fedn Eur. biochem. Socs Lett.
(1984)
KimuraC. et al.
A novel peptide which stimulates adenylate cyclase: molecular cloning and characterization of the ovine and human cDNAs
Biochem. biophys. Res. Commun.
(1990)
MiyataA. et al.
Isolation of a novel 38 residue hypothalamic polypeptide which stimulates adenylate cyclase in pituitary cells
Biochem. biophys. Res. Commun.
(1989)
MiyataA. et al.
Isolation of a neuropeptide corresponding to the N-terminal 27 residues of the pituitary adenylate cyclase activating polypeptide with 38 residues (PACAP 38)
Biochem. biophys. Res. Commun.
(1990)
OgiK. et al.
Molecular cloning and characterization of cDNA for the precursor of rat pituitary adenylate cyclase activating polypeptide (PACAP)
Biochem. biophys. Res. Commun.
(1990)
RobberechtP. et al.
Immunoreactive helodermin-like peptides in rat: a new class of mammalian neuropeptides related to secretin and VIP
Biochem. biophys. Res. Commun.
(1985)
RobberechtP. et al.
Interaction of synthetic N- and C-terminal fragments of helodermin with rat liver VIP receptors
Peptides
(1986)
SundlerF. et al.
Is helodermin produced by medullary thyroid carcinoma cells and normal C-cells? Immunocytochemical evidence
Regul. Pept.
(1988)
AbsoodA. et al.
Neuropeptides of the VIP/helodermin/PACAP family elevate plasma cAMP in mice: comparison with a range of other regulatory peptides
Regul. Pept.
(1991)

There are more references available in the full text version of this article.

Cited by (236)

Overviews of avian neuropeptides and peptides
2022, Sturkie's Avian Physiology
Peptides play significant roles in diverse physiological processes. This chapter provides a brief review on 134 peptides/neuropeptides, divided under 39 families. This covers their structure, functions, expression and major actions involved in the regulation of avian growth, stress, food intake, energy balance, lipid and glucose metabolism, reproduction, water homeostasis, calcium homeostasis, cardiovascular functions, blood pressure, host defense, etc., in a systemic approach. Most of these avian peptides have their corresponding mammalian orthologs, and some of them play physiological roles similar to those in mammals, such as hypothalamic GHRH and SST, stimulate, and inhibit pituitary GH secretion, respectively. However, notable differences are present between these two animal groups, so caution must be taken when we transfer our knowledge on mammalian peptides onto avian models. The unique physiological and behavioral processes such as flight, brooding in birds warrant in-depth investigation to uncover the roles of these peptides in avian model and across vertebrates from a comparative endocrinological perspective.
Characteristic of galaninergic components of the enteric nervous system in the cancer invasion of human large intestine
2012, Annals of Anatomy
Citation Excerpt :
The literature in the field contains some papers dealing with the chemical coding of the intramural neurons in the mammalian gastrointestinal tract. In general, GAL is present in the elements of the enteric nervous system, in both the neurons and in the nerve fibers of the submucosal and myenteric plexuses of the human colon (Ferri et al., 1983, 1988; Wattchow et al., 1988; Hoyle and Burnstock, 1989a,b; Burleigh and Furness, 1990; Domoto et al., 1990; Crowe et al., 1992; Sundler et al., 1992; Furness et al., 1995), and in the small intestine and colon of the guinea pig and the pig (Ekblad et al., 1985; Melander et al., 1985; Furness et al., 1987; Timmermans et al., 1992, 1997; Bartness et al., 2001). GAL was found to be a neurotransmitter, in both non-cholinergic and cholinergic secreto-motor neurons and in vasodilatory neurons.
This study presents changes that take place in galanin (GAL)-containing components of the enteric nervous system in patients with colorectal carcinoma. The main goal of our study was to investigate the morphological and biochemical characteristics of the GAL-ergic neurons and nerve fibers in the cancer-affected part of the colon and to compare results to the unchanged part of the intestine.
The study was performed on tissue samples collected from 15 patients (9 women and 6 men). The material was collected during surgery, i.e., resection of the anterior sigmoid colon and anterior amputation of the rectum, from patients in good general condition, without any other significant disease. Immunohistochemistry and ELISA were used to study, respectively, the distribution of neurons and nerve fibers containing GAL and concentration of this neuropeptide in the human large intestine during the colorectal cancer infiltration.
Morphological examinations have revealed that a statistically significantly higher percentage of GAL+ neurons (46%) was observed in the pathologically changed myenteric plexuses as compared to the unchanged part of the intestine (35%). No changes were observed in the density of GAL+ nerve fibers in the submucosal and myenteric plexuses. Biochemical examinations performed with the ELISA revealed that the average GAL content in the cancer tissues was 9.38 ng/g versus 12.27 ng/g in the morphologically unchanged tissues (the difference was statistically significant).
The results indicate the continuous presence of GAL-ergic innervation in the immediate vicinity of the cancer invasion, which may be attributed to increased contraction of the affected part of intestine.
Postpyloric Gastrointestinal Peptides
2012, Physiology of the Gastrointestinal Tract, Two Volume Set
Postpyloric Gastrointestinal Peptides
2012, Physiology of the Gastrointestinal Tract
Pituitary adenylate cyclase-activating peptide (PACAP) immunoreactivity distribution in the small intestine of the adult New Hampshire chicken
2011, Acta Histochemica
We conducted a study in which we demonstrated by means of immunoperoxidase and immunofluorescence methods the presence of pituitary adenylate cyclase-activating peptide 38 (PACAP-38) immunoreactivity in the small intestine of adult New Hampshire chickens and its co-localization with VIP. In particular we describe for the first time the presence of PACAP-positive cells in the epithelium of crypts and villi. Using double immunostaining, we observed that these two peptides were widely co-localized in the nerve structures of duodenum and jejunum with the exception of the ileum, where we noticed a faint co-localization regarding the nerve fibers of the lamina propria of the villi. Furthermore, the two peptides were occasionally co-stored in the epithelial cells of the mucosa. Our findings suggest that in the chicken small intestine, PACAP can be considered, not only as a neuromodulator released by nerve elements, but also as a gut hormone secreted by endocrine cells, and it appears likely to have a role in the regulation of important intestinal physiological functions.
Contribution of endogenous nitrergic and peptidergic influences to the altered neurally-induced gastric contractile responses in strips from dystrophic (mdx) mice
2010, Regulatory Peptides
Gastrointestinal motor disorders have been reported to occur in dystrophic (mdx) mice. The aim of the present study was to investigate the contribution of endogenous nitrergic and peptidergic components to the gastric contractile responses in strips from wild type (WT) and mdx mice. In both preparations, electrical field stimulation (EFS) induced frequency-dependent excitatory responses that were abolished by atropine or tetrodotoxin. The amplitude of the neurally-induced contractile responses was greater in strips from mdx mice in respect to the WT ones. In both preparations, at the end of the stimulation period strip tension decayed below the pre-stimulus level (off-relaxations). The nitric oxide (NO) synthesis inhibitor L-NNA increased the amplitude of the EFS-induced contractile responses without influencing off-relaxations. α-chymotrypsin and PACAP 6–38 abolished off-relaxations and also caused a reduction in amplitude of the contractile responses, whereas VIP receptor antagonists were ineffective. The efficacy of L-NNA, α-chymotrypsin or PACAP 6–38 on the excitatory responses was lower in strips from mdx mice in respect to the WT ones. α-chymotrypsin, in the presence of L-NNA, was no longer able to decrease the amplitude of the neurally-induced contractile responses but still abolished off-relaxations in both preparations. Direct muscular responses to methacholine were similar in amplitude in the two preparations and were not influenced by L-NNA or α-chymotrypsin. The results indicate that both endogenous NO and peptides influence the EFS-induced cholinergic responses: a stronger peptidergic modulatory action on a weaker nitrergic neurotransmission is suggested to occur in strips from mdx mice in respect to the WT ones and to contribute to the altered gastric contractile responses.

View all citing articles on Scopus

View full text

Pituitary adenylate cyclase activating peptide: A novel vasoactive intestinal peptide-like neuropeptide in the gut

Abstract

Neuroscience

Fedn Eur. biochem. Socs Lett.

Biochem. biophys. Res. Commun.

Biochem. biophys. Res. Commun.

Biochem. biophys. Res. Commun.

Biochem. biophys. Res. Commun.

Biochem. biophys. Res. Commun.

Peptides

Regul. Pept.

Neuropeptides of the VIP/helodermin/PACAP family elevate plasma cAMP in mice: comparison with a range of other regulatory peptides

Regul. Pept.