ANTAGONISTIC REGULATION OF ALPHA(2)-ADRENOCEPTORS BY NEUROPEPTIDE-Y RECEPTOR SUBTYPES IN THE NUCLEUS-TRACTUS-SOLITARII

The modulation of alpha(2)-adrenoceptors by neuropeptide Y Y-1 and neu ropeptide Y Y-2 receptor subtypes has been studied in the nucleus trac tus solitarii of the male rat. The autoradiographical experiments show ed that neuropeptide Y-(1-36), neuropeptide Y-(13-36), a selective neu ropeptide Y Y-2 receptor agonist, and [Leu(31),Pro(34)]neuropeptide Y, a selective neuropeptide Y Y-1 receptor agonist, in the nanomolar ran ge increased the K-d value of the [H-3]p-aminoclonidine binding sites in the above rank order of potency without changing the B-max values. In contrast, in the competition experiments, the neuropeptide Y Y-1 an d the neuropeptide Y Y-2 receptor agonists decreased and increased, re spectively, with the same potency the IC50 value of l-adrenaline and e specially of clonidine for the alpha(2)-adrenoceptor agonist binding s ites associated with an increase and a decrease of the B-0 value, resp ectively. Cardiovascular experiments showed that microinjections of cl onidine into the nucleus tractus solitarii induced dose-dependent vaso depressor and bradycardiac responses. Threshold doses for vasodepresso r effects of neuropeptide Y-(1-36) and of the neuropeptide Y Y-1 recep tor agonist and for vasopressor effects of the neuropeptide Y Y-2 rece ptor agonist significantly counteracted the vasodepressor action elici ted by an ED(50) dose of clonidine in the nucleus tractus solitarii, t he bradycardiac action of clonidine also being counteracted by the neu ropeptide Y Y-2 but not the neuropeptide Y Y-1 receptor agonist. The p resent results give indications for the existence of an antagonistic m odulation of high affinity alpha(2)-adrenoceptors by the neuropeptide Y Y-1 and neuropeptide Y Y-2 receptor subtype in the nucleus tractus s olitarii which may contribute to a reduction of alpha(2)-adrenoceptor- mediated cardiovascular depression.