THE EFFECT OF NEUROPEPTIDE-Y ON SODIUM, CHLORIDE AND POTASSIUM-TRANSPORT ACROSS THE RAT DISTAL COLON

1 Neuropeptide Y (NPY; 10(-10)-10(-7) mol l(-1)) reduced basal short-circuit current (I-sc) in a concentration-dependent manner in the rat distal colon but was ineffective in the proximal colon. 2 The action of NPY was dependent upon the presence of Cl- and HCO3- anions and was blocked by prior treatment of the tissue with a Cl- channel blocker. The decrease in I-sc was associated with an increase in mucosa-to-serosa fluxes of Na+, Rb+ (K+) and Cl-, whereas the serosa-to-mucosa flux of Cl- was decreased. 3 The size of the inhibitory NPY effect was linearly correlated with the height of the basal I-sc, i.e. it inhibited 55% of basal secretory I-sc. 4 The action of NPY was unaffected by indomethacin and tetrodotoxin, when given alone, but was abolished, when the basal I-sc was decreased to values near zero by a combination of both inhibitors. This inhibition could be overcome by restoring basal I-sc with prostaglandin E(2), indicating that the effect of NPY is not mediated by nerves or prostaglandins, but that NPY is only effective, when anion secretion is stimulated by the spontaneous release of neurotransmitters and prostaglandins. 5 NPY inhibited the increase in I,, induced by veratridine and prostaglandin E(2), but it had no effect on the I-sc induced by direct stimulation of the adenylate cyclase with forskolin, or on I-sc induced by stimulation of the Ca2+-pathway with carbachol. Inhibition of the response to veratridine or prostaglandin E(2) by NPY showed the same dependence on the height of the I-sc just prior to addition of NPY as seen in control conditions, i.e. NPY inhibited 55% of cyclic AMP-mediated secretion. 6 These results suggest that the effect of NPY is mediated by an inhibition of cyclic AMP-stimulated secretion, which is stimulated in the rat distal colon by a continuous release of prostaglandins and neurotransmitters.