Evidence for different pre-and post-junctional receptors for neuropeptide Y and related peptides.

The effects of neuropeptide Y (NPY), peptide YY (PYY), desamido-NPY and five C-terminal fragments of NPY or PYY were tested on different smooth muscle preparations in vitro. The fragments were NPY 19-36, NPY 24-36, PYY 13-36, PYY 24-36 and PYY 27-36. NPY and PYY appear to exert three principally different effects at the level of the sympathetic neuroeffector junction. Firstly, they have a direct post-junctional effect, leading to constriction of certain blood vessels; this was studied on the guinea-pig iliac vein. Secondly, they potentiate the response to various vasoconstrictors; this was studied on the rabbit femoral artery and vein, using noradrenaline and histamine, respectively, as agonists. Thirdly, NPY and PYY act prejunctionally in that they suppress the release of noradrenaline from sympathetic nerve endings upon stimulation; this was studied in the rat vas deferens. NPY and PYY were approximately equipotent in constricting the guinea-pig iliac vein, while desamido-NPY and the fragments were without effect. Desamido-NPY and the fragments were ineffective also in potentiating the response to noradrenaline in the rabbit femoral artery, nor did they potentiate the response to histamine in the rabbit femoral vein. NPY and PYY potentiated the response to noradrenaline in the artery, as well as the response to histamine in the vein. The NPY- and PYY-induced suppression of noradrenaline release from the prostatic portion of the rat vas deferens was reproduced by PYY 13-36 but not by the shorter fragments nor by desamido-NPY. In conclusion, a C-terminal portion seems to be sufficient for exerting the prejunctional effect of NPY and PYY, while the whole sequence seems to be required for post-junctional (direct and modulatory) effects. An amidated C-terminal is crucial for maintaining the biological activity of NPY. Desamido-NPY and the fragments that were inactive as agonists also seemed inactive as antagonists.