Inhibition of neuropeptide Y-induced potentiation of noradrenaline-induced vasoconstriction by PP56 (D-myo-inositol 1,2,6-tris-phosphate).

1. Although neuropeptide Y (NPY) is a potent vasoconstrictor in many vascular beds, nanomolar concentrations of this peptide potentiate the noradrenaline-induced contractions in rabbit gastroepiploic and femoral arteries, and guinea-pig mesenteric and uterine arteries. 2. The potentiating effect of NPY on noradrenaline-induced contraction was present in endothelium-denuded femoral arteries. 3. The potentiating effect of NPY on noradrenaline-induced contraction was antagonized by PP56 (D-myo-inositol 1,2,6-trisphosphate) in low concentrations (down to 0.1 nM). This antagonistic effect was observed in all four types of vessels studied. Contractions induced by noradrenaline, histamine, endothelin-1 and potassium were not altered by PP56 in concentrations upto 1 microM in femoral artery of rabbit. 4. We provide evidence that a non-peptide (PP56) can selectively antagonize NPY-induced effects in rabbit and guinea-pig peripheral arteries without affecting the vasoconstrictor response to noradrenaline.