Tachykinin-induced increase in gastric mucosal resistance: role of primary afferent neurons, CGRP, and NO.
The tachykinins [Ala5,beta-Ala8]neurokinin A-(4-10) {[Ala5,beta-Ala8]NKA-(4-10)} and NKA-(4-10) dose dependently protected against ethanol-induced gastric mucosal damage in rats (half-maximal inhibitory dose, 46 and 48 nmol/kg, respectively). These effects were abolished by primary afferent nerve denervation, calcitonin gene-related peptide (CGRP) immunoneutralization, the CGRP receptor antagonist human (h) hCGRP-(8-37), and inhibition of nitric oxide (NO) biosynthesis by NG-nitro-L-arginine methyl ester. 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]NKA-(4-10) and NKA-(4-10), whereas 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 after primary afferent nerve stimulation by capsaicin.
Stroff
T
T
Department of Experimental Clinical Medicine, Ruhr-University of Bochum, Germany.
Plate
S
S
Ebrahim
J S
JS
Ehrlich
K H
KH
Respondek
M
M
Peskar
B M
BM
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000502:physiology*; D003714:Denervation; D000431:Ethanol / Q000633:toxicity; D006801:Humans; D007413:Intestinal Mucosa / Q000294:innervation / Q000473:pathology / Q000502:physiology*; D008297:Male; D009475:Neurons, Afferent / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D015320:Tachykinins / Q000494:pharmacology*
D015320:Tachykinins; D009569:Nitric Oxide; D000431:Ethanol; D015740:Calcitonin Gene-Related Peptide