Depressor Effect of Intrathecal Neuropeptide Y (NPY) Is Mediated by Y2 Subtype of NPY Receptors

The effect of intrathecal administration of neuropeptide Y (NPY), NPY COOH-terminal fragments as well as an NPY Y1 receptor ligand on arterial blood pressure (ABP) of anesthetized rat was studied. NPY and all NPY COOH-terminal fragments tested (NPY11-36, NPY14-36 and NPY18-36), believed to act through Y2 receptors produced a dose-related depressor effect (with slight differences in potency) after intrathecal administration. However, intrathecal injection of a reputed NPY Y1 ligand [Leu31,Pro34]-NPY, did not alter arterial pressure significantly. The results suggest that intrathecal NPY produces its depressor effect through activation of Y2 receptors. To test whether these NPY fragments behaved as antagonists or partial agonists, we examined effect of coadministration of NPY and NPY fragments on the depressor effect of NPY. Coadministration of an equimolar dose (0.1 nmol) of NPY and NPY14-36 or NPY18-36 did not change the depressor effect of intrathecal NPY. When a 10-times higher dose (1 nmol) of the NPY fragments was used, the depressor effect of NPY was still not altered, suggesting that the fragments tested did not possess antagonistic effects. We conclude that the depressor effect of intrathecal NPY is mediated primarily by an NPY Y2 receptor subtype.