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 neuropeptide Y, its selective neuropeptide Y Y-1 receptor analogue, [Leu(31),Pro(34)]neuropeptide Y, and the Y-2-selective C-terminal fragment, neuropeptide Y-(18-36), on basal and electrically evoked noradrenaline overflow in the portal vein as well as on mean arterial pressure and heart rate were investigated in permanently instrumented freely moving rats. Neuropeptide Y dose dependently (2-2000 ng/kg/min) attenuated the electrically evoked noradrenaline overflow and almost complete blockade was reached at the highest dose used. [Leu(31),Pro(34)]Neuropeptide Y also dose dependently (20-20000 ng/kg/min) attenuated the evoked overflow, 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 due 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 coexistence of Y-1 and Y-2 receptors, in the portal vein of freely moving rats, which in conjunction are able to inhibit markedly electrically evoked noradrenaline overflow. Postjunctional neuropeptide Y receptors mediating an increase in blood pressure in the freely moving rat are solely of the Y-1 subtype.