Inhibitory action of neuropeptide Y on agonist-induced responses in isolated guinea pig trachea.

The effect of neuropeptide Y (NPY) was tested on isolated guinea pig trachea. At 30 nM, NPY induced a weak but significant contractile response which was on average less than 6% of responses elicited by standard spasmogens. This myotropic action of NPY was blocked by indomethacin. In addition to its contractile activity, NPY greatly reduced the maximal response to vasoactive intestinal peptide (VIP), noradrenaline (NA), substance P (SP) and 5-hydroxytryptamine (5-HT), without affecting their pD2 values. However, NPY did not influence the response induced by histamine and carbamylcholine. Pretreatment of tracheal spirals with indomethacin (10(-6) M) abolished the NPY-evoked inhibition of VIP, SP and 5-HT responses but failed to reduce the action of NPY on NA-elicited relaxation. This latter effect was however blocked in the presence of tetrodotoxin. In conclusion, NPY inhibits responses elicited by various agonists in the guinea pig trachea. This effect seems to be mediated at both pre- and postjunctional levels. The postjunctionally mediated inhibitory action of NPY appears to be expressed especially with agents that generate prostaglandins concomitantly with inducing their response. In contrast, the NPY-evoked inhibition of NA-evoked relaxation seems to be mediated via a prejunctional mechanism.