SELECTIVE MODULATION OF THE NPY RECEPTORS OF THE Y-2 SUBTYPE BY ALPHA(2) RECEPTORS IN THE NUCLEUS-TRACTUS-SOLITARII OF THE RAT - A CARDIOVASCULAR AND QUANTITATIVE RECEPTOR AUTORADIOGRAPHICAL ANALYSIS

The modulation of neuropeptide Y (NPY) receptors by alpha(2) receptors in the nucleus tractus solitarii (Sol) of the rat was evaluated using quantitative receptor autoradiography and measurements of mean arteri al blood pressure and heart rate. The receptor autoradiographical expe riments showed that clonidine (10 nM), a selective alpha(2) receptor a gonist, induced a 59% increase in the B-0 value and a 47% decrease in the IC50 value of NPY(1-36) when competing for [I-125]peptide YY([I-12 5]PYY)-binding sites in the presence of [Leu(31), Pro(34)]NPY (100 nM) , a selective NPY Y-1 receptor agonist, to block the binding to NPY Y- 1 receptors. In contrast, when NPY(13-36) (300 nM), a selective NPY Y- 2 receptor agonist, was used to block the binding to NPY Y-2 receptors , clonidine (1-30 nM) did not affect the B-0 value and the IC50 value of NPY(1-36) when competing for [I-125]PYY-binding sites, suggesting t hat the stimulation of alpha(2) receptors can selectively increase the affinity of NPY(1-36) for the NPY Y-2 receptor. Microinjections of th reshold doses of adrenaline or clonidine into the Sol not only counter acted the vasopressor action of a close to ED(50) dose of coinjected N PY(13-36), but also changed the vasopressor and tachycardic response p roduced by NPY(13-36) into a vasodepressor and bradycardic response. H owever, threshold doses of adrenaline or of clonidine microinjected in to the Sol did not modify the vasodepressor responses to a close to ED (50) dose of NPY(1-36) or of [Leu(31), Pro(34)]NPY. Therefore, the pre sent results indicate the existence of an antagonistic alpha(2)-NPY Y- 2 receptor interaction in the Sol, which may lead to an uncoupling of the NPY Y-2 receptor associated with an increase in affinity and a dom inance of NPY transduction over the NPY Y-1 receptor.