Biological relevance of pituitary adenylate cyclase-activating polypeptide (PACAP) in the gastrointestinal tract.

This study investigated whether toxin B of Clostridium difficile can activate human submucosal neurons and the involved pathways. Isolated segments of human colon were placed in organ culture for 3...

Toxin B of Clostridium difficile activates human VIP submucosal neurons, in part via an IL-1β-dependent pathway

Guanylin, an activator of the guanylyl cyclase C receptor in the apical membrane of intestinal epithelium, modulates intestinal fluid and electrolyte transport. The bioactive 15-amino acid peptide originally isolated from rat intestine represents the C-terminal part of a longer, 115-residue prepropeptide. The aim of the present study was to characterize the direction and molecular form in which guanylin is secreted from the colonic mucosa, as well as the mechanisms that trigger its secretion. Isolated rat colonic mucosa was mounted in Ussing chambers, allowing the separate determination of apical and basolateral release. After HPLC purification, two different molecular forms of guanylin were identified in the apical incubation media by combining a bioassay for guanylyl cyclase C activation, a specific guanylin enzyme-linked immunosorbent assay and mass spectrometry, as well as sequence analysis: a bioactive form coeluting with synthetic 15-residue guanylin and the 94-residue propeptide, guanylin-22-115. The basal concentration of proguanylin at the apical side of epithelia was about 15-fold higher, compared with that of the small, bioactive peptide. In the basolateral incubation media, no proguanylin and only very low amounts of bioactive guanylin were detected. Incubation with carbachol led to a significant increase of about 7-fold in the release of proguanylin to both sides of the isolated epithelia. On the apical side, a concomitant increase of the small, bioactive peptide was observed; whereas, on the basolateral side, its concentration remained unchanged. Vasoactive intestinal peptide or the NO-donor S-nitroso-N-acetylpenicillamine did not affect guanylin secretion. Our results suggest that, in the intestine, guanylin is secreted mainly to the luminal side of the epithelium. The peptide is released as a 94-residue propeptide, which is then processed to a smaller, bioactive form (luminocrine secretion). Carbachol stimulates the release of proguanylin to both sides of the intestinal mucosa, but a parallel increase in the bioactive C-terminal derivative only occurs on the apical side. In vivo, the basolateral release could be a source of circulating proguanylin, which might be processed proteolytically to the active peptide in distant target tissues (endocrine secretion).

/pdf/regulated-side-directed-secretion-of-proguanylin-from-2mtoyjvrfl.pdf

Regulated, side-directed secretion of proguanylin from isolated rat colonic mucosa.

This study reports on changes in the pituitary adenylate cyclase-activating peptide 27-like immunoreactive (PACAP-27-LI) nerve structures of the enteric nervous system (ENS) in the porcine descending colon, caused by chemically induced inflammation, nerve injury, and proliferative enteropathy (PE), which is a “natural” inflammation of the porcine digestive tract. The distribution pattern of PACAP-27-LI structures was studied using the immunofluorescence technique in the circular muscle layer, enteric plexuses (i.e., myenteric plexus (MP), outer submucous plexus (OSP), and inner submucous plexus (ISP)), and in the mucosal layer. Under physiological conditions, PACAP-27-LI perikarya have been shown to constitute 4.04 ± 0.66, 6.66 ± 0.77, and 11.19 ± 0.74 % in the MP, OSP, and ISP, respectively. Changes in PACAP-27 immunoreactivity depended on the pathological factor studied. The numbers of the PACAP-27-LI perikarya amounted to 12.26 ± 1.43, 12.28 ± 0.79, and 21.13 ± 1.19 % in chemically induced colitis, 17.83 ± 0.88, 9.03 ± 1.05, and 20.72 ± 1.35 % during PE and 10.65 ± 0.82, 6.88 ± 1.04, and 14.04 ± 1.09 % after axotomy in MP, OSP, and ISP, respectively. All of the studied processes generally resulted in an increase in the number of PACAP-27-LI nerve fibers in the circular muscle and mucosal layers. The obtained results suggest that PACAP-27-LI nerve structures of ENS may participate in various pathological states within the porcine descending colon, and their functions probably depend on the type of pathological factor.

Changes in Pituitary Adenylate Cyclase-Activating Peptide 27-Like Immunoreactive Nervous Structures in the Porcine Descending Colon During Selected Pathological Processes

© 2004 by Taylor & Francis Group, LLC. This chapter focuses on neuromuscular and neuroepithelial transmission in the intestine. There seems to be an ever increasing number of putative neurotransmitters in the enteric nervous system, but relatively few have a defined role in either neuromuscular or neuroepithelial transmission even though their chemical coding may have been established. In addition to covering the “old” classic transmitters, acetylcholine and noradrenaline, some more novel candidate transmitters such as endothelin and pituitary adenylate cyclase-activating polypeptide are discussed, as well as the “modern” classical transmitters ATP and vasoactive intestinal polypeptide (VIP), and the notso- classical nitric oxide. Co-transmission is a widespread phenomenon in the enteric nervous system and particularly with regard to inhibitory transmission, it is difficult to discuss one transmitter, such as ATP, in isolation from others such as nitric oxide and VIP. An area of current research is the plasticity of the enteric nervous system, and how expression of neurotransmitters changes in response to ageing, trauma, surgery or chronic drug treatment, and what the mechanisms underlying these changes are. Some pathological conditions are considered, namely diabetes mellitus, idiopathic chronic constipation, Hirschsprung’s disease and ulcerative colitis, in all of which intestinal neuromuscular transmission may be affected.

Neuroeffector Transmission in the Intestine

To investigate the effects of PACAP-27 on electrolyte transport across the isolated human intestinal mucosa, changes in short-circuit current (Isc) were measured in Ussing chamber experiments. Serosally added PACAP-27 increased Isc in a concentration-dependent manner, eliciting a similar maximal effect in both the jejunal and the colonic mucosa. Bumetanide inhibited Isc responses, indicating stimulation of Cl- secretion. The potency and efficacy of PACAP-27 were comparable to those of VIP, suggesting that both peptides activate intestinal secretion by way of a common receptor located in the basolateral membrane of the intestinal epithelium.

Pituitary Adenylate Cyclase-Activating Polypeptide: A Potent Activator of Human Intestinal Ion Transporta

Handle everyday research tasks with reliable, citation-backed results

Your personal Research Agent to handle research tasks with citation-backed results

Popular Tasks used by Researchers

How can I help with your research?

Meet SciSpace

Get more enhanced response by uploading the PDFs you want me to reference.

No relevant PDFs in your library

SciSpace is the AI research assistant for academics. Run systematic literature reviews on 280M+ papers, and write papers with cited sources. Trusted by 1M+ students, PhDs & researchers.

SciSpace | AI for Research

Analyze PDFs

Code & Manuscripts

Funding & Grants

Literature & Patents

Medical & Clinical Data

Systematic Review

Visualize & Present

Web & Data

Build a Google Scholar-like website for your research.

Build a website

Create charts and images for your research

Create a Chart

Write a paper for submission to a journal

Draft a manuscript

Patent Search

Design eye-catching scientific posters in minutes.

Scientific Poster Generation

Systematic Literature Review

One task is running at the moment. Your messages will be shown right after.

Drag and drop or click here to browse

Loved by <highlight>1 million+</highlight> researchers

Extract a list of specific topics and their sources from unstructured text

Topics

Compare and analyze relevant papers that matches with your search

Papers

Get insights from PDFs and bookmarked papers from your library

My library

Recent searches

Try searching for:

Catch AI-generated content in scholarly and non-scholarly content

{ai} Detector

Ai Writer

Get PDF Summaries, highlighted text explanations 

Chat with PDF

Effortlessly create in-text citations and bibliographies in APA and 2,500 other formats

Citation generator

Get explanations, summaries, and answers on academic papers

Ease up your research workflow with {scispace}'s cohort of exciting AI tools

Elevate your academic writing skills and convey your ideas the way you want

Paraphraser

Explore our range of reading and writing tools

Your file is being prepared and should be ready in a few minutes. If it's a large file, it might take a bit longer. You can close this window, and we'll email you the file when it's done.

You have reached a maximum limit of <strong>{limit}</strong> columns in the table. Remove at least <strong>1</strong> column to add or create another one.

H. R. Raab

Author Tools

Chat about Author

Papers

Pituitary Adenylate Cyclase-Activating Polypeptide: A Potent Activator of Human Intestinal Ion Transporta