MAST-CELL AMINES AND INOSINE-INDUCED VASOCONSTRICTION IN THE RAT HIND-LIMB

UNDER Certain circumstances injected inosine causes a net vasoconstric tive effect on the arterioles, which has been attributed to 5-hydroxy- tryptamine (5HT) released in response to adenosine type 3 (A(3)) recep tor stimulation of mast cells residing in the adventitia, We have soug ht further evidence for this hypothesis using blood vessels of the rat hind limb perfused in vitro at constant rate with a gelatin-containin g physiological salt solution, Injection of inosine (2.7 mg) caused a rise in perfusion pressure, which was only slightly increased by inclu sion of N-nitro-L-arginine methyl ester (100 mu M) in the perfusate, I nclusion in the perfusate of cyproheptadine (1 mu M), compound 48/80 ( 1 mu g/ml), 8-phenyltheophylline (1 mu M) or 8-cyclopentyl-1,3 dipropy lxanthine (0.1 mu M) greatly reduced the presser response to inosine, The presser effect of injected 5HT (400 mu g) was abolished by pre-tre atment with cyproheptadine, but not by pre-treatment with compound 48/ 80, These results suggest that the net presser response to injected in osine was mainly the result of an Al receptor-mediated release of 5HT, most probably from mast cells, No evidence was found for an involveme nt of A(3) receptor stimulation.