Characterization of the receptor response for the neuropeptide Y-evoked suppression of parasympathetically-mediated contractions in the guinea pig trachea

Abstract

Neuropeptide Y (NPY) acts via several distinct receptor types. The aim of the present study was to examine which NPY receptors are coupled to inhibition of parasympathetically-mediated contractions of the isolated guinea pig trachea. Electrical field stimulation of tracheal rings evoked a rapid twitch, which was abolished by atropine (1 microM). NPY, the structurally related hormone peptide YY (PYY), the Y2 receptor agonist [Cys2, Aoc5-24, D-Cys27]NPY, as well as NPY 5-36 and NPY 13-36 evoked a concentration-dependent inhibition of the electrically-stimulated twitches. Pretreatment with the Y1 receptor-selective antagonist BIBP3226 (1 microM) failed to prevent the NPY-induced inhibition. Although less potent than NPY, the Y1 (and Y4-Y6) receptor agonist [Leu31, Pro34]NPY also inhibited the electrically-stimulated twitches. Another NPY-related peptide, pancreatic polypeptide, which recognizes Y4-Y6 receptors did not affect the stimulated twitches at concentrations up to 1 microM. However, pretreatment with the Y1 receptor-selective antagonist BIBP3226 (1 microM) virtually abolished the inhibition evoked by [Leu31, Pro34]NPY. None of the peptides affected the baseline tension and BIBP3226 (1 microM) per se did not affect the amplitude of the electrically-stimulated twitches. In conclusion, it seems that NPY and PYY are capable of suppressing parasympathetically mediated contractions in the guinea pig trachea mainly via Y2 receptors, but there is also a small contribution from Y1 receptors.