Pituitary adenylate cyclase-activating polypeptide inhibits the cyclooxygenase pathway of rat cerebral microvessels

The presence of nerve endings containing pituitary adenylate cyclase-activa ting polypeptide (PACAP) and vasoactive intestinal polypeptide (VIP) around cerebral microvessels suggests that these peptides have regulatory roles i n the cerebral microcirculation. Prostanoids synthesized by the cerebrovasc ular endothelium have a determining role in the regulation of the brain cir culation. In the present study, the effects of PACAP and VIP on the cycloox ygenase pathway of cerebral microvessels were investigated. The isolated mi crovessels were incubated with 1-C-14-arachidonic acid and different concen trations of the peptides. The prostanoids formed were separated by means of overpressure thin-layer chromatography, and were quantitatively determined by liquid scintillation. Higher concentrations (10(-7) and 10(-6) mol L-1) of PACAP significantly inhibited the activity of the cyclooxygenase pathwa y, whereas VIP had no significant effect on it. As regards the cyclooxygena se metabolites, the syntheses of thromboxane Ag and prostaglandin Dp were i nhibited significantly. PACAP and VIP are known to increase the intracellul ar cAMP level in the cerebral microvessels and in the present experiments t he protein kinase A inhibitor H-89 attenuated the effect of PACAP on prosta noid synthesis. It is concluded that the cyclooxygenase pathway of rat cere bral microvessels is more sensitive to PACAP than to VIP. The inhibitory ef fect of PACAP on prostanoid synthesis is mediated via a cAMP-dependent path way. By inhibiting the formation of vasoactive prostanoids, PACAP can decre ase the vasoreactivity of the microvessels.