Role of peptidergic sensory neurons in gastric mucosal blood flow and protection.
The present findings have revealed a new aspect of how mechanisms of gastric mucosal resistance to injury are called into effect and are coordinated by the nervous system. Capsaicin-sensitive sensory neurons in the stomach play a physiological role in monitoring acid influx into the superficial mucosa. Once activated, they strengthen gastric mucosal defense against deep injury, with a key process in this respect being an increase in blood flow through the gastric mucosa. This concept opens up completely new perspectives in the physiology and pathophysiology of the gastric mucosa if we consider that the long-term integrity of the gastric mucosa may be under the subtle control of acid-sensitive sensory neurons and that, vice versa, improper functioning of these neutral control mechanisms may predispose to gastric ulcer disease. The present observations also indicate that some of the peptides contained in gastric sensory nerve endings might fulfill a transmitter or mediator role in controlling gastric mucosal blood flow and integrity. Whereas substance P and neurokinin A are unlikely to play a role in the regulation of gastric mucosal blood flow, there is severalfold evidence that CGRP is very important in this respect. This peptide, which in the rat gastric mucosa originates exclusively from spinal sensory neurons, is released upon stimulation of sensory nerve endings and is extremely potent in facilitating gastric mucosal blood flow and in protecting the mucosa from injurious factors. Selective ablation of spinal sensory neurons containing CGRP weakens the resistance of the gastric mucosa against acid injury, which is most likely due to inhibition of protective vasodilator reflexes. We now aim at providing direct pharmacological evidence that antagonism of endogenously released CGRP results in similar pathophysiological consequences as ablation of capsaicin-sensitive sensory neurons.
Holzer
P
P
Department of Experimental and Clinical Pharmacology, University of Graz, Austria.
Lippe
I I
II
Raybould
H E
HE
Pabst
M A
MA
Livingston
E H
EH
Amann
R
R
Peskar
B M
BM
Peskar
B A
BA
Taché
Y
Y
Guth
P H
PH
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000502:physiology*; D002211:Capsaicin / Q000494:pharmacology; D005753:Gastric Mucosa / Q000098:blood supply / Q000294:innervation / Q000502:physiology*; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology*; D009479:Neuropeptides / Q000502:physiology*; D012039:Regional Blood Flow
D009479:Neuropeptides; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin