Neuropeptide Y (NPY) and its homolog, peptide YY, are present respectively in neurons and endocrine cells within the mammalian small intestine. In this study, we examined the actions of NPY on ion transport in the porcine distal jejunum mucosasubmucosa in vitro. Peptide YY and NPY were equieffective in producing rapid and sustained decreases in basal short-circuit current (Isc), a bioelectrical measure of active ion transport, eliciting half-maximal decreases at respective serosal concentrations of 0.8 and 30 nmol/l. NPY-induced changes in Isc were due to increased mucosa-to-serosa and net Cl fluxes and were not affected by the absence of extracellular HCO3 ions. NPY activity was correlated with the magnitude of the basal Isc and appeared to depend on the spontaneous production of eicosanoids. The peptide also decreased Isc stimulated by forskolin and 8-bromo-cyclic AMP, but the ionic bases for this effect were complex and differed from those determined under basal conditions. NPY attenuated increases in Isc produced by electrical stimulation of enteric neurons with an IC50 = 5 nmol/l. The actions of the peptide on basal and cyclic AMP-induced ion transport were abolished by the neuronal conduction blocker tetrodotoxin, but not by the opiate antagonist naloxone. The α-adrenoceptor blocker phentolamine diminished the effects of NPY on basal, but not cyclic AMP-induced Isc. These results indicate that NPY is capable of modulating NaCl transport in the porcine jejunal mucosa under several different conditions. Furthermore, the effects of the peptide are mediated in part through noradrenergic nerves as well as enteric neurons of unknown chemical identity.
Bibliographical noteFunding Information:
The authors thank Drs. Keith R. Hildebrand and Francis L. Quito for experimental assistance in aspects of this investigation and Dr. Scott M. O'Grady for critically reviewing this manuscript and for technical advice. This investigation was funded in part by U.S.P.H.S. grants No. DK-37497 and BSRG S07-RR0593, Minnesota Agricultural Experiment Station grants MN-61-063 and MN-61-038 and funding by the Minnesota Pork Producers Association to D.R.B. The Minnesota Veterinary Medical Council provided funding in support of S.L.B.M.F.O. was recipient of a New Investigator award from the Comparative Gastroenterology Society.
- Chloride ion absorption
- Distal jejunum
- Enteric nervous system
- Neuropeptide Y
- Sodium ion secretion