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.