CHARACTERIZATION OF VASCULAR POSTSYNAPTIC NPY RECEPTOR FUNCTION AND REGULATION AND DIFFERENTIAL SENSITIVITY OF Y(1) AND Y(2) RECEPTOR FUNCTION TO CHANGES IN EXTRACELLULAR CALCIUM AVAILABILITY AND PRIOR IN-VITRO PEPTIDE EXPOSURE

Effects of calcium-free buffer, nifedipine, or prior cumulative neurop eptide Y (NPY) receptor agonist concentration exposure on vasoconstric tive responsiveness to the agonists were assessed in norepinephrine (N E)-conditioned isolated rat femoral artery rings. Calcium-free buffer and nifedipine partially inhibited responsiveness to initial NPY expos ure; residual responsiveness to NPY re-exposure was unaffected. In con trast, these treatments markedly inhibited responsiveness to the Y2 ag onist NPY13-36, the calcium channel agonist BAY K 8644 (BAY) and the p artial alpha, adrenoceptor agonist indanidine but did not alter that t o the Y, agonist [Leu31, Pro34]NPY. Responsiveness to NPY and NPY13-36 but not to BAY or indanidine was markedly reduced 120 min following c onditioning regardless of prior ring exposure to the same peptide; onl y prior exposure reduced responsiveness to [LeU31, Pro34]NPY. Responsi veness changes to NPY at various times or after various numbers of NE and/or NPY exposures indicated that pre-exposure and time-related resp onsiveness reductions were discriminable and temporally unrelated to c onditioning. Postsynaptic vascular Y2 receptor activation therefore ac counts for the known sensitivity of NPY-induced pressor and vasoconstr ictive actions to nifedipine. The 'time-dependent' loss of Y2 receptor function may also explain prior failures to observe postsynaptic arte rial Y2 receptors in vitro.