Alpha-trinositol blocks the inhibitory effects of NPY on dilatation to forskolin but not the adenylyl cyclase activity induced by NPY or forskolin in guinea-pig cerebral vessels.

There is much data showing correlation between forskolin-induced relaxation and production of cyclic AMP. But are these processes coupled or two phenomena occurring in parallel? This question was studied in guinea-pig cerebral vessels by using NPY as a strong inhibitor and alpha-trinositol as its antagonist. The basal cyclic AMP content of cerebral vessel segments in the control group was 670 +/- 53 fmol/mg wet weight (w.w.). Forskolin (10(-7), 3 x 10(-7) and 10(-6) M) increased the formation of cyclic AMP to 738 +/- 86 (ns), 699 +/- 81 (ns) and 1158 +/- 132 fmol/mg w.w. (p < 0.05), respectively. alpha-trinositol (10(-8)-10(-6) M) neither reduced the formation of cyclic AMP compared to basal cyclic AMP levels nor affected the forskolin-stimulated increase of cyclic AMP (p > 0.05). On the other hand, NPY (10(-7) M) not only decreased basal formation of cyclic AMP (p < 0.05) but also attenuated the forskolin-stimulated increase of cyclic AMP (p < 0.005). The inhibitory effects of NPY on both basal levels of cyclic AMP and forskolin-induced increase of cyclic AMP were not reversed by the application of alpha-trinositol (10(-8)-10(-6) M). In studies on vasomotor responses, forskolin (10(-9)-10(-5) M) induced a concentration-dependent relaxation of precontracted guinea-pig basilar arteries. NPY (10(-7) M) shifted the forskolin-induced relaxation of the basilar arteries towards higher forskolin concentrations. This inhibitory effect of NPY was reversed by alpha-trinositol (10(-6) M). We conclude that 1) NPY decreases basal and forskolin-stimulated cyclic AMP levels; 2) alpha-trinositol neither reverses the inhibitory effect of NPY on nor modulates basal or forskolin-stimulated cyclic AMP levels; 3) However, the antagonistic effect of NPY on forskolin-induced relaxation is significantly reversed by administration of alpha-trinositol. This demonstrates a dissociation of the dilator effects of forskolin and its generation of cyclic AMP.