Tachykinin-induced increase in gastric mucosal resistance: role of
primary afferent neurons, cgrp and no.
Stroff, Thomas, Susanne Plate, Jalal Seyed Ebrahim, Karl-Heinz
Ehrlich, Michael Respondek, and Brigitta M. Peskar.
Departments of Experimental Clinical Medicine and Pathology, Ruhr
-University of Bochum, D-44780 Bochum, Germany
APStracts 3:0114G, 1996.
The tachykinins (Ala5,[beta]Ala8)?NKA4-10 and NKA4-10 dose-dependently
protected against ethanol-induced gastric mucosal damage in rats
(ID50, 46 and 48?nmol/kg, respectively). These effects were abolished
by primary afferent nerve denervation, calcitonin gene-relat ed
peptide (CGRP) immunoneutralization, the CGRP receptor antagonist
hCGRP8-37 and inhibition of nitric oxide (NO) biosynthesis by NG
-nitro-L-arginine methyl ester (L-NAME). Tachykinin-induced protection
occurred despite marked depression of gastric mucosal blood flow and
was not associated with increased acid secretion. NK2 receptor
blockade antagonized the protective effects of (Ala5,[beta]Ala8)
NKA4-10 and NKA4-10, while NK1 receptor blockade was ineffective.
Blockade of NK2 but not NK1 receptors prevented by 65% the protection
evoked by topical capsaicin without affecting capsaicin-induced
hyperemia. We conclude that the increase in gastric mucosal
resistance evoked by tachykinins is NK2 receptor-mediated and
involves primary afferent neurons, CGRP and NO. Gastric mucosal
hyperemia and increased acid secretion do not participate in the
effect. Tachykinins activating NK2 receptors contribute to the
increase in gastric mucosal resistance but not the increment in
mucosal blood flow following primary afferent nerve stimulation by
capsaicin.
Received 16 January 1996; accepted in final form 21 May 1996.
APS Manuscript Number G23-6.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 28 June 96