Evidence for mast cell, leukotriene and nitric oxide involvement in the regulation of the adrenoceptor number of inflamed small intestine in guinea pigs.
Changes in the populations of neurotransmitter receptors involved in the control of intestinal smooth muscle function have been associated with the altered motility of the inflamed gut. Thus, trinitrobenzenesulphonic acid (TNBS)-induced gut inflammation is accompanied by an increase in alpha- and a decrease in beta-adrenoceptor numbers in guinea pig small intestine. In the present study, we investigated the effects of anti-inflammatory compounds (cyclooxygenase inhibitor indomethacin, lipooxygenase inhibitor MK-886, nitric oxide synthase inhibitor NG-nitro-L-arginine methylester (L-NAME), mast cell stabilizer doxantrazole) on TNBS-induced adrenoceptor changes. Smooth muscle adrenoceptor populations, labelled by subtype-specific radioligands 6 days after TNBS, were significantly different from those of sham-treated controls: alpha 1- and alpha 2-adrenoceptor numbers increased by more than 50%, while beta-adrenoceptor numbers decreased by more than 50%. These changes, associated with severe inflammation as assessed histologically and by myeloperoxidase assay, were prevented by doxantrazole or L-NAME, and only partly by MK-886. In contrast, indomethacin did not prevent these changes. It appears then that: (a) mast cell mediators, nitric oxide and leukotrienes are likely to contribute to TNBS-induced changes in adrenoceptor populations in the guinea pig inflamed intestine; (b) there is no evidence for prostanoid involvement in this process. It was suggested that changes in smooth muscle adrenoceptor populations may be an important mechanism by which gut inflammation alters intestinal motility.
INRA, Department of Pharmacology & Toxicology, Toulouse, France.
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Martinolle
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Garcia-Villar
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Bueno
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D004751:Enteritis / Q000473:pathology / Q000503:physiopathology*; D006168:Guinea Pigs; D007421:Intestine, Small / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D015289:Leukotrienes / Q000502:physiology*; D008297:Male; D008407:Mast Cells / Q000502:physiology*; D009130:Muscle, Smooth / Q000378:metabolism; D009569:Nitric Oxide / Q000502:physiology*; D009195:Peroxidase / Q000378:metabolism; D011941:Receptors, Adrenergic / Q000187:drug effects / Q000378:metabolism*
D000893:Anti-Inflammatory Agents; D015289:Leukotrienes; D011941:Receptors, Adrenergic; D009569:Nitric Oxide; D009195:Peroxidase