Growth hormone secretagogue receptors in rat and human gastrointestinal tract and the effects of ghrelin

The peptide hormone ghrelin is known to be present within stomach and, to a lesser extent, elsewhere in gut. Although reports suggest that gastric function may be modulated by ghrelin acting via the vagus nerve, the gastrointestinal distribution and functions of its receptor, the growth hormone secr...

Full description

Saved in:
Bibliographic Details
Published in:Neuroscience 2003-01, Vol.120 (2), p.443-453
Main Authors: Dass, N.B, Munonyara, M, Bassil, A.K, Hervieu, G.J, Osbourne, S, Corcoran, S, Morgan, M, Sanger, G.J
Format: Article
Language:English
Subjects:
Animals
Atropine - pharmacology
Biological and medical sciences
CHO Cells
Colon - cytology
Colon - drug effects
Colon - metabolism
Cricetinae
Dose-Response Relationship, Drug
enteric nervous system
Evoked Potentials - drug effects
Evoked Potentials - physiology
Female
Fundamental and applied biological sciences. Psychology
gastric fundus
Gastric Mucosa - metabolism
gastro prokinetic
Ghrelin
Green Fluorescent Proteins
Humans
Immunohistochemistry - methods
Luminescent Proteins - metabolism
Motor control and motor pathways. Reflexes. Control centers of vegetative functions. Vestibular system and equilibration
Muscarinic Antagonists - pharmacology
Muscle Contraction - drug effects
Muscle Contraction - physiology
Nerve Fibers - metabolism
Peptide Hormones - pharmacology
Peptides - immunology
Peptides - metabolism
Rabbits
Rats
Receptors, Cell Surface - immunology
Receptors, Cell Surface - metabolism
Receptors, G-Protein-Coupled
Receptors, Ghrelin
sigmoid colon
Stomach - cytology
Stomach - drug effects
Transfection - methods
Vertebrates: nervous system and sense organs
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The peptide hormone ghrelin is known to be present within stomach and, to a lesser extent, elsewhere in gut. Although reports suggest that gastric function may be modulated by ghrelin acting via the vagus nerve, the gastrointestinal distribution and functions of its receptor, the growth hormone secretagogue receptor (GHS-R), are not clear and may show signs of species-dependency. This study sought to determine the cellular localisation and distribution of GHS-R-immunoreactivity (-Ir) using immunofluorescent histochemistry and explore the function of ghrelin in both human and rat isolated gastric and/or colonic circular muscle preparations in which nerve-mediated responses were evoked by electrical field stimulation. The expression of GHS-R-Ir differed to a greater extent between species than between gut regions of the same species. Both the human and rat gastric and colonic preparations ( n=3 each) expressed GHS-R-Ir within neuronal cell bodies and fibres, cells associated with gastric glands and putative entero-endocrine and/or mast cells. Smooth muscle cells and epithelia were devoid of GHS-R-Ir and only rat preparations expressed GHS-R-Ir on nerve fibres associated with the muscle layers. GHS-R-Ir was fully competed in all cases in pre-adsorption studies and antiserum specificity was confirmed using a cell line transiently expressing the rat GHS-R. In rat isolated forestomach circular muscle, ghrelin 0.1–10 μM had no effect on smooth muscle tension but concentration-dependently facilitated the amplitude of contractions evoked by excitatory nerve stimulation ( n=4–7; P0.05 each) and human ascending ( n=3) and sigmoid ( n=1) colon, these concentrations of ghrelin were without effect ( P>0.05 each). The data suggest that ghrelin has the potential to profoundly affect gastrointestinal functions in both species and at least one of these functions is to exert a gastric prokinetic activity. Moreover, we suggest that this activity of ghrelin is mediated via the enteric nervous system, in addition to known vagus nerve-dependent mechanisms.
ISSN:0306-4522
1873-7544
DOI:10.1016/S0306-4522(03)00327-0