THE RABBIT SAPHENOUS-VEIN - A TISSUE-PREPARATION SPECIFICALLY ENRICHED IN NPY-Y1 RECEPTOR SUBTYPE

Neuropeptide Y (NPY), a co-transmitter in noradrenergic sympathetic ne rves of the cardiovascular system, was tested on isolated segments of rabbit saphenous vein. NPY caused strong, long lastening and concentra tion dependent contraction resistant to adrenergic blockade. PYY, a NP Y related peptide, shared this property. As pressor agents, both pepti des were about 100-fold more potent than norepinephrine and at their h ighest concentrations caused a contraction of a similar magnitude as N E. Gradual shortening of N-terminal end of the NPY molecule caused maj or loss of potency and reduction of intrinsic activity; which suggests that the entire molecule is required to produce full biological activ ity in this vascular preparation. Addition of [Leu31,Pro34]pNPY, a NPY analog with specific agonist properties at Y1 receptors, mimicked the effect of NPY whereas NPY (13-36), a selective agonist at Y2 receptor s, caused a 2 log unit shift to the right of the concentration respons e curve. These results suggest that the vasoconstrictor effect of NPY in rabbit saphenous vein results from a direct effect on smooth muscle cells and that the receptors involved are of the Y1 subtype.