alpha-Trinositol blocks neuropeptide Y-induced inositolphosphate formation in cerebral vessels

Neuropeptide Y (NPY) induces contraction of guinea-pig basilar arteries via activation of Y1 receptors. This contraction is blocked by D-myo-inositol-1,2,6-triphosphate (alpha-trinositol). Previous binding studies have shown that alpha-trinositol has no effect at Y1 or Y2 binding sites thus the antagonistic effect should occur at the level of a second messenger. We have examined the effects of NPY on the formation of inositol phosphates (IP) and have looked for an antagonistic effect of alpha-trinositol. NPY (10(-9)-3 x 10-(-7) M) induced strong concentration-dependent contraction of basilar arteries from young guinea-pigs (weight 200-250 g) (Emax: 76.4 +/- 11.1%) but not of arteries from old guinea-pigs (weight > 500 g) (Emax: 2.8 +/- 1.5%). [Pro34]NPY and PYY induced contraction of similar magnitude and potency, whereas NPY13-36 had only a weak effect. This demonstrates an effect via the Y1 type of NPY receptor. The contraction induced by NPY was blocked by alpha-trinositol (p < 0.05). LiCI (2 x 10-4) M), used to inhibit IP breakdown, had no effect on the contraction induced by NPY. NPY (10(-10)-10(-8) M) increased the formation of IP in cerebral vessels from young guinea-pigs from 357 +/- 48 cpm/mg w.w. to 900 +/- 233 cpm/mg w.w. However, there was no alteration in IP formation in cerebral vessels from old guinea-pigs (NPY 10(-9)-10(-7) M). In the presence of alpha-trinositol (10(-8)-10(-6) M) the NPY induced stimulation of IP formation was totally abolished.(ABSTRACT TRUNCATED AT 250 WORDS)