Inhibition of antigen-induced muscle contractions by inhibitors of thromboxane pathway in rat small intestine

Rats were sensitized against egg albumin and the response of the longitudinal muscle from the proximal small intestine to the antigen was tested. Egg albumin (1-100 mu g/ml) concentration-dependently induced a contraction of the longitudinal muscle in tissues from sensitized animals but not from nonsensitized animals. The response to the antigen was resistant to neuronal blockers like tetrodotoxin, atropine and hexamethonium. Inhibitors of thromboxane synthesis such as the cyciooxygenase inhibitor, indomethacin, the thromboxane synthase blocker, 1-benzylimidazole, or the combined cyclooxygenase/lipoxygenase/thromboxane synthase inhibitor, sulfasalazine, inhibited the contraction evoked bg egg albumin. A similar concentration-dependent inhibition of the antigen response was observed with tno thromboxane A(2) receptor blockers, SK&F 88046 and KW-3635. None of these blockers affected the response to the muscarinic agonist, carbachol, excluding unspecific effects of the drugs on smooth muscle contractility. The effect of antigen was reduced by the mast cell stabilizing agent, quercetin, and by the histamine H-1 receptor blocker, mepyramin. These drugs, however, also inhibited the response to carbachol. When contractions were stimulated directly by the stable thromboxane derivative, carbocyclic thromboxane A(2), the smooth muscle proved to be more than three orders of magnitude more sensitive to this agonist of the thromboxane pathway compared to histamine. Consequently, thromboxane hz seems to be one of the main mediators of anaphylactically induced longitudinal muscle contractions in the rat small intestine.