EFFECT OF NEUROPEPTIDE-Y ON BRADYKININ-INDUCED RELEASE OF PROSTACYCLIN AND THROMBOXANE FROM GUINEA-PIG PERFUSED LUNG

We have previously reported that neuropeptide Y (NPY) inhibits respons es induced by various agonists (noradrenaline, vasoactive intestinal p eptide, substance P,5-hydroxytryptamine) in isolated guinea pig trache a. Although the underlying mechanisms have not been fully characterize d, it was found that the NPY-evoked inhibition was specifically expres sed with agents for which locally released prostaglandins (PGs) are im portant determinants for their myotropic activity. In the present stud y, we have extended these findings by examining whether NPY was capabl e of regulating the release of prostacyclin and thromboxane A,induced by bradykinin (BK) from naive and ovalbumin-sensitized guinea pig perf used lungs. Our results showed that infusion of NPY (0.24 mu M) throug h the lung significantly inhibited the release of 6-keto-PGF(1 alpha) (>30%) and thromboxane B-2 (50%) induced by intraarterial administrati on of BK (3 mu g) from untreated and ovalbumin-sensitized guinea pig p erfused lung. However, the inhibitory effect of NPY was lost in the im munological production of prostaglandins. These results suggest that N PY may act as a regulatory agent of the release of cyclooxygenase-deri ved products by possibly acting on events preceding phospholipase A(2) activation.