Neuropeptide Y 22-36

Heterogeneity among NPY (and PYY) receptors was first proposed on the basis of studies on sympathetic neuroeffector junctions, where NPY (and PYY) can exert three types of action: 1) a direct (e.g., vasoconstrictor) response; 2) a postjunctional potentiating effect on NE-evoked vasoconstriction; and 3) a prejunctional suppression of stimulated NE release; the two latter phenomena are probably reciprocal, since NE affect NPY mechanisms similarly. It was found that amidated C-terminal NPY (or PYY) fragments, e.g., NPY 13-36, could stimulate selectively prejunctional NPY/PYY receptors, which were termed Y2-receptors. Consequently, the postjunctional receptors which were activated poorly by NPY/PYY fragments, were termed Y1-receptors. Later work has indicated that the Y2-receptor may occur postjunctionally in selected sympathetic effector systems. The central nervous system appears to contain a mixture of Y1- and Y2-receptors as indicated by functional as well as binding studies. For instance, NPY and NPY 13-36 produced diametrically opposite effects on behavioral activity, indicating the action of the parent peptide on two distinct receptors. Cell lines, most importantly neuroblastomas, with exclusive populations of Y1- or Y2-receptors, have been characterized by binding and second messenger studies. In this work, selective agonists for the two receptor subtypes were used. Work of many investigators has formed the basis for subclassifying NPY/PYY effects being mediated by either Y1- or Y2-receptors. A preliminary subclassification based on effects of NPY, PYY, fragments and/or analogs is provided in Table 6. It is, however, to be expected that further receptor heterogeneity will be revealed in the future. It is argued that mast cells possess atypical NPY/PYY receptors. The histamine release associated with stimulation of the latter receptors may, at least in part, underlie the capacity of NPY as well as of short C-terminal fragments to reduce blood pressure. Fragments, such as NPY 22-36, appear to be relatively selective vasodepressor agents because of their weak vasopressor properties.(ABSTRACT TRUNCATED AT 400 WORDS)

It has been suggested that the family of neuropeptide Y (NPY) peptides is a promising target for the neuroprotective therapy; therefore, knowledge of the structure of these biologically active compounds and their behavior at solid/liquid interface is important in order to design new analogues. Because there is still a lack of detailed information on the behavior of NPY and its mutated analogues at the solid/liquid interfaces, in this work surface-enhanced Raman spectroscopy (SERS) analysis was used to investigate NPY and its native NPY3-36, NPY13-36, and NPY22-36and mutated acetyl-(Leu28,31)-NPY24-36C-terminal fragments, acting on Y2receptors (Y2R), in order to determine their possible metal surface/molecule interactions. In these studies, colloidal gold nanoparticle surface served as a solid surface, whereas an aqueous solution was used as a liquid medium. The observed differences in the band intensities, wavenumbers, and widths allowed us to draw conclusions on an adsorption mode of NPY and on changes in this mode upon the shortening of the peptide chain and increase in solution pH (from pH 3 to pH 11). Briefly, three different species of Tyr were identified onto the colloidal gold surface depending upon the length of the peptide chain and solution pH. Tyrosine (TyrOH) is present in a basic medium. Tyrosinate (TyrO-) is present in an acidic solution, whereas phenoxyl radical (Tyr*) appears at neutral pH for peptides having relatively short peptide chain (acetyl-(Leu28,31)-NPY24-36). The elongation of the peptide chain partially (NPY13-36and NPY22-36) or completely (NPY3-36and NPY) protects the Tyr residue against conversion to the radical form.

1. Neuropeptide Y (NPY) and peptide YY (PYY) seem to act on at least two receptor subtypes, Y1 and Y2. The Y1-receptor requires the whole C-terminally amidated NPY/PYY molecule whereas the Y2-receptor in addition recognizes C-terminal fragments of the two peptides. The present study was designed to elucidate whether NPY and related peptides were able to release histamine from isolated peritoneal mast cells of the rat. 2. NPY, NPY 15-36, NPY 22-36, NPY 26-36 and desamido-NPY evoked a concentration-dependent release of mast-cell histamine. The pEC15 values for NPY 15-36 and NPY 22-36 were higher, while the pEC15 value for NPY 26-36 was lower than that for NPY. At the highest concentration tested (0.1 mM), NPY and its C-terminal fragments released between 30 and 40% of the total histamine content. At the same concentration desamido-NPY released about 20%. 3. PYY and PYY 15-36 also evoked a concentration-dependent release of mast-cell histamine. PYY was more effective than PYY 15-36 since, at 0.1 mM, PYY released about 33%, while PYY 15-36 released about 15% of the total histamine content. Pancreatic polypeptide (PP) and the Y1-receptor-selective agonist [Pro34]NPY were virtually inactive. 4. The effect profile of the NPY/PYY-related peptides suggests that they act on the mast cells by a mechanism that does not involve either of the receptor subtypes hitherto described. The kinetics of the NPY-evoked histamine release may suggest that positively charged amino acid residues of NPY/PYY release mast-cell histamine by a non-receptor mechanism, as has been suggested for substance P and other basic peptides.