CANINE LIVER RELEASES NEUROPEPTIDE-Y DURING SYMPATHETIC-NERVE STIMULATION

To determine whether the liver or gut releases neuropeptide Y (NPY) fr om their sympathetic nerves, we performed bilateral thoracic sympathet ic nerve stimulation (BTSNS) in halothane-anesthetized dogs and calcul ated gut and liver NPY spillover. BTSNS markedly increased hepatic NPY spillover (Delta = +32 +/- ng/min) and arterial NPY concentration (De lta = +220 +/- 56 pg/ml), despite no effect on gut NPY spillover (Delt a = +8 r 7 ng/min). To determine the liver's contribution to this incr ease of circulating NPY, hepatic nerves were selectively stimulated (H NS). Liver NPY spillover increased markedly (Delta = -114 +/- 42 ng/mi n, P < 0.025) during HNS, causing a large increase of arterial NPY (De lta = +586 +/- 237 pg/ml, P < 0.025). Using this ratio of liver spillo ver to arterial increments of NPY, we calculated that the liver makes a major contribution (70%) to circulating NPY levels during BTSNS. The predominant form of canine NPY coeluted with synthetic [Met(17)]NPY a nd the minor form of canine NPY coeluted with the oxidized form of [Me t(17)]NPY on high-performance liquid chromatography. We therefore conc lude that dog NPY is likely [Met(17)]NPY and that the liver, rather th an the gut, is a major source of circulating NPY during sympathetic ne rve stimulation and perhaps stress.