The differential mechanisms of mild irritants on adaptive cytoprotection.
The protective action of mild irritants has been established. However, the mechanisms as to how they antagonize the injurious action produced by the subsequent challenge with an ulcerogenic stimulus are still unclear. The present study examined the different protective mechanisms of an oral administration of the three mild irritants, 20% ethanol, 0.3 mol/L HCl or 5% NaCl against the gastric injurious actions of absolute ethanol in rats. In an attempt to clarify the pathways and mediators involved in the adaptive cytoprotection, [D-Pro2, D-Trp7,9]-substance P (substance P antagonist), Nw-nitro-L-arginine methyl ester (L-NAME), indomethacin, capsaicin, lidocaine, atropine or hexamethonium was given. The protective action of 20% ethanol but not the other two mild irritants, was antagonized by L-NAME, indomethacin and capsaicin, which are the inhibitors of nitric oxide (NO) and prostaglandins (PG) synthesis, and afferent sensory neuron blocker, respectively. Substance P antagonist, lidocaine or atropine given alone, prevented mucosal damage; however, only substance P antagonist enhanced the anti-lesion action of 20% ethanol, while atropine and lidocaine increased the protective effect of NaCl and HCl. The three mild irritants increased the residual gastric secretion. Only 20% ethanol and 5% NaCl but not 0.3% HCl significantly increased the basal adherent mucus and also attenuated the mucus depletion by absolute ethanol. It is concluded that the cytoprotective action of either ethanol or NaCl seems to be mediated through the increase of residual gastric secretion and adherent mucus. In the ethanol-treated group, these actions could act through the afferent sensory fibres, with NO and PG as the possible mediators.(ABSTRACT TRUNCATED AT 250 WORDS)
Cho
C H
CH
Department of Pharmacology, Faculty of Medicine, University of Hong Kong.
Ko
J K
JK
Tang
X L
XL
D000222:Adaptation, Physiological; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001285:Atropine / Q000494:pharmacology; D002211:Capsaicin / Q000494:pharmacology; D006063:Chorionic Gonadotropin / Q000494:pharmacology*; D000431:Ethanol / Q000494:pharmacology* / Q000633:toxicity; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018738:Hexamethonium / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007509:Irritants / Q000494:pharmacology*; D008012:Lidocaine / Q000494:pharmacology; D008297:Male; D009093:Mucus / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology; D011453:Prostaglandins / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012965:Sodium Chloride / Q000494:pharmacology*; D013276:Stomach Ulcer / Q000503:physiopathology / Q000517:prevention & control; D013373:Substance P / Q000037:antagonists & inhibitors
D006063:Chorionic Gonadotropin; D007509:Irritants; D011453:Prostaglandins; D009569:Nitric Oxide; D013373:Substance P; D018738:Hexamethonium; D000431:Ethanol; D012965:Sodium Chloride; D001285:Atropine; D001120:Arginine; D008012:Lidocaine; D002211:Capsaicin; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin