Neuropeptide Y antagonistic properties of D-myo-inositol-1.2.6-trisphosphate in guinea pig basilar arteries.

The antagonistic properties on neuropeptide Y (NPY)-induced contraction of the guinea pig basilar artery of D-myo-inositol-1.2.6-triphosphate (PP56) has been examined using a sensitive in vitro system. It was observed that PP56 did not per se cause contraction or relaxation of precontracted vessel segments. However, it was found to be a non-competitive antagonist of NPY-induced contraction. This effect was observed in the concentration range 10(-8)-10(-6) M PP56. A slight potentiation of endothelin I-induced contraction was seen at high concentrations (10(-3) M). In contrast there was no modulation of the contractile effects elicited by bradykinin, noradrenaline, 5-hydroxytryptamine (5-HT) or prostaglandin F2 alpha (PGF2 alpha) apart from a slight reduction in maximum effect at 10(-4) M and 10(-3) M PP56. PP56 was observed to possess antihistaminic and anticholinergic properties in the concentration range 10(-5) M-10(-3) M. The relaxant effects of vasoactive intestinal peptide, calcitonin gene-related peptide, neurokinin A and substance P were only modified to a minor extent by PP56 in concentrations of 10(-4) M and 10(-3) M. In conclusion, PP56 appears to be the first non-peptide which potently and rather selectively antagonizes NPY-induced contractions of the guinea pig basilar artery. In high concentrations, PP56 may modify the responses of other agents tested, including histamine and acetylcholine.