D-MYO-INOSITOL 1,2,6-TRISPHOSPHATE BLOCKS NEUROPEPTIDE Y-INDUCED FACILITATION OF NORADRENALINE-EVOKED VASOCONSTRICTION OF THE MESENTERIC BED

Perfusion of the rat mesenteric bed with 0.1 or 10 nM neuropeptide Y p otentiated the noradrenaline-induced increase in mesenteric pressure; the peptide did not modify basal perfusion pressure. While perfusion w ith 0.1 nM neuropeptide Y significantly increased the maximal noradren aline-evoked vasoconstriction without modifying its EC50, 10 nM neurop eptide Y potentiated the maximal noradrenaline effect and significantl y shifted its concentration-response curve to the left. Perfusion with 1-10 muM D-myo-inositol 1,2,6-trisphosphate (alpha-trinositol) reduce d, in a concentration-dependent fashion, the neuropeptide Y-induced po tentiation of the noradrenaline-evoked vasoconstriction without alteri ng the potency or maximal response evoked by the catecholamine alone. Perfusion with 0.1 nM neuropeptide Y plus 1 muM alpha-trinositol compl etely abolished the neuropeptide Y-induced facilitation of the noradre naline effect. Alpha-Trinositol 1 muM in the presence of 10 nM neurope ptide Y caused a nonparallel rightward shift of the noradrenaline conc entration-response curve as compared to that obtained in the presence of 10 nM neuropeptide Y alone. The alpha-trinositol blockade of the fa cilitatory action of neuropeptide Y was reversible.