Role of leukotriene C4 in mucosal damage caused by necrotizing agents and indomethacin in the rat stomach.

Intragastric ethanol stimulates mucosal formation of leukotriene C4 in the rat stomach. The present study demonstrates that the increase in leukotriene C4 formation begins within 30 seconds and is maximal within 5 minutes, closely paralleled by the appearance of hemorrhagic lesions. Leukotriene C4 formation returns to prechallenge levels within 3 hours, although erosions still persist.

Release of calcitonin gene-related peptide induced by capsaicin in the vascularly perfused rat stomach.

It has been suggested that capsaicin-induced gastric mucosal protection results from the local release of vasodilator peptides such as calcitonin gene-related peptide (CGRP) from afferent nerve endings within the stomach, since CGRP is able to reduce gastric lesion formation. This concept is supported by the present finding that capsaicin (10(-5) M), administered to the vascularly perfused stomach of the rat, produces a more than 30-fold rise of the CGRP content of the venous effluent. High-pressure liquid chromatography revealed only one peak of immunoreactivity coeluting with synthetic CGRP.

Effects of non-steroidal anti-inflammatory drugs on rat gastric mucosal leukotriene C4 and prostanoid release: relation to ethanol-induced injury.

1. The effects of oral and subcutaneous administration of the non-steroidal anti-inflammatory drugs sodium salicylate, aspirin and indomethacin on ex vivo gastric mucosal release of leukotriene C4 (LTC4) prostaglandin E2 (PGE2), 6-oxo-PGF1 alpha and thromboxane B2 (TXB2) were investigated in rats under basal conditions as well as after challenge with ethanol. 2.

Possible mode of action of 5-aminosalicylic acid.

Despite the extensive use of sulfasalazine (SAS) and/or 5-aminosalicylic acid (5-ASA) in patients with inflammatory bowel disease and, more recently, rheumatoid arthritis, their mode of action has not been elucidated so far. None of the numerous pharmacological and biochemical effects described, including immunosuppressive, antifolate, and modulatory actions on lymphocyte and leukocyte functions, could be defined unequivocally as mediating their beneficial activity. Recently, interest has focused on actions of SAS and 5-ASA on the various enzymes of the arachidonic acid cascade.