HETEROGENEITY OF PREJUNCTIONAL NEUROPEPTIDE-Y RECEPTORS INHIBITING NORADRENALINE OVERFLOW IN THE PORTAL-VEIN OF FREELY MOVING RATS

The effects of intraportal infusions of different doses of neuropeptid e Y, its selective neuropeptide Y Y-1 receptor analogue, [Leu(31),Pro( 34)]neuropeptide Y, and the Y-2-selective C-terminal fragment, neurope ptide Y-(18-36), on basal and electrically evoked noradrenaline overfl ow in the portal vein as well as on mean arterial pressure and heart r ate were investigated in permanently instrumented freely moving rats. Neuropeptide Y dose dependently (2-2000 ng/kg/min) attenuated the elec trically evoked noradrenaline overflow and almost complete blockade wa s reached at the highest dose used. [Leu(31),Pro(34)]Neuropeptide Y al so dose dependently (20-20000 ng/kg/min) attenuated the evoked overflo w, reaching a maximum of 55% inhibition at the highest dose (20000 ng/ kg/min). Neuropeptide Y-(18-36) attenuated the evoked release only at 20000 ng/kg/min (by 46%). Only at the highest dose did neuropeptide Y (2000 ng/kg/min) and [Leu(31),Pro(34)]neuropeptide Y (20000 ng/kg/min) significantly enhance mean arterial pressure and decrease heart rate and basal plasma noradrenaline levels, the latter two effects being du e to the baroreceptor reflex. Neuropeptide Y-(18-36) did not influence these parameters at all doses used. The results indicate the presence of prejunctional neuropeptide Y Y-1 receptors, and possibly the coexi stence of Y-1 and Y-2 receptors, in the portal vein of freely moving r ats, which in conjunction are able to inhibit markedly electrically ev oked noradrenaline overflow. Postjunctional neuropeptide Y receptors m ediating an increase in blood pressure in the freely moving rat are so lely of the Y-1 subtype.