lithium-chloride and Stomach-Ulcer

This study compares the involvement of ATP-sensitive potassium (K(ATP)) channels and prostaglandins in various forms of gastroprotection in the rat. Instillation of 1 ml of 70% ethanol induced severe gastric mucosal damage (lesion index 39 +/- 0.8), which was substantially but not maximally reduced by oral pretreatment with 16,16-dimethyl-prostaglandin (PG) E(2) (75 ng/kg), 20% ethanol (1 ml), sodium salicylate (15 mg/kg), the metal salt lithium chloride (7 mg/kg), the sulfhydryl-blocking agent diethylmaleate (5 mg/kg), and the thiol dimercaprol (10 mg/kg). Administration of indomethacin (20 mg/kg) increased gastric mucosal damage induced by 70% ethanol (lesion index 45 +/- 0.8) and significantly reduced the protective effect of 20% ethanol, sodium salicylate, lithium chloride, diethylmaleate, and dimercaprol. The blocker of K(ATP) channels glibenclamide (5-10 mg/kg) significantly antagonized the protective effect of 16,16-dimethyl-PGE(2), 20% ethanol, sodium salicylate, lithium chloride, diethylmaleate, and dimercaprol. The inhibition of protection induced by glibenclamide was reversed by pretreatment with the K(ATP) channel activator cromakalim (0.3-0.5 mg/kg). In conclusion, our results indicate a role of K(ATP) channels in the gastroprotective effect of 16,16-dimethyl-PGE(2) and of the other agents tested. Since the protection afforded by these agents is additionally indomethacin-sensitive, it is suggested that under these conditions endogenous prostaglandins act as activators of K(ATP) channels, and this mechanism, at least in part, mediates gastroprotection.

Topics: 16,16-Dimethylprostaglandin E2; Adaptation, Physiological; Adenosine Triphosphate; Administration, Oral; Animals; ATP-Binding Cassette Transporters; Dimercaprol; Dose-Response Relationship, Drug; Ethanol; Gastric Mucosa; Glyburide; KATP Channels; Lithium Chloride; Male; Maleates; Potassium Channel Blockers; Potassium Channels; Potassium Channels, Inwardly Rectifying; Prostaglandins; Rats; Rats, Wistar; Sodium Salicylate; Stomach Ulcer

Increasing evidence indicates that thyrotropin-releasing hormone (TRH), and endogenous brain-gut peptide may play a role in experimental ulcerogenesis. Potential interactions between TRH and imipramine (a typical tricyclic antidepressant (TCA] on the development of TRH-induced gastric lesions have not been investigated. Imipramine (0.05, 0.5 and 5 mg/kg, i.p.) dose-dependently inhibited gastric lesion formation induced by intracisternal (i.c.) administration of TRH (1 micrograms). In addition, imipramine (5 mg/kg, i.p.) significantly decreased gastric acid secretion in response to i.c. TRH (1 microgram) in rats with pyloric ligation. These findings suggest the TCAs may be effective drug agents against centrally initiated gastric ulcerations. The mechanism of this response probably involves blockade of cholinergic (muscarinic) and H2 histamine receptors.

Topics: Animals; Brain; Chlorides; Dose-Response Relationship, Drug; Gastric Acid; Gastric Mucosa; Imipramine; Lithium; Lithium Chloride; Male; Rats; Rats, Inbred Strains; Stomach Ulcer; Thyrotropin-Releasing Hormone