Vasoconstrictor effects of various neuropeptide Y analogues on the rat tail artery in the presence of phenylephrine.

1. The increase in perfusion pressure induced by neuropeptide Y (NPY), peptide YY (PYY) and related peptides were compared in the perfused rat tail artery precontracted by a submaximal concentration (1 microM) of the vasoconstrictor, phenylephrine. 2. NPY, PYY, [Leu31,Pro34]NPY, [Glu16,Ser18,Ala22,Leu28,31]NPY (ESALL-NPY) and the centrally truncated and stabilized analogues [D-Cys5,8-aminooctanoic acid7-20, Cys24]-NPY (D-Cys5-NPY) and [D-Cys7, 8-aminooctanoic acid8-17,Cys20]-NPY (D-Cys7-NPY) produced a concentration-dependent enhancement of the vasoconstrictor response induced by 1 microM phenylephrine. PYY was two times more potent than NPY and [Leu31,Pro34]NPY while ESALL-NPY, D-Cys7-NPY and D-Cys5-NPY were approximately 3, 5 and 16 times less potent than NPY respectively. NPY, D-Cys5-NPY and D-Cys7-NPY gave similar maximal responses whereas those observed for PYY, [Leu31,Pro34]NPY and ESALL-NPY were much greater than that of NPY. 3. NPY 13-36 and [des-Ser3,Lys4,Cys2,8-aminooctanoic acid3-24, D-Cys27]-NPY ([es-Ser3,Lys4]Cys2-NPY) were practically inactive at concentrations up to 3 microM, whereas [des-Ser3,Lys4,D-Cys2,8-aminooctanoic acid3-24,Cys27]-NPY ([des-Ser3,Lys4]D-Cys2-NPY), which differs from [des-Ser3,Lys4]Cys2-NPY in the disulphide bridge (a D-Cys in position 2 for [des-Ser3,Lys4]D-Cys2-NPY instead of an L-CYs for [des-Ser3,Lys4]Cys2-NPY) was a weak agonist the maximal effect of which could not be ascertained. 4. The contractile effects of [des-Ser3,Lys4]D-Cys2-NPY were additive with those of NPY and [Leu31,Pro34]NPY demonstrating that it is not a partial agonist but may simply not interact competitively with the receptor binding site for NPY.(ABSTRACT TRUNCATED AT 250 WORDS)