ABSTRACT
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 mucosa-submucosa 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 alpha-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.
Subject(s)
Cyclic AMP/metabolism , Electrolytes/metabolism , Jejunum/drug effects , Neurons/drug effects , Neuropeptide Y/pharmacology , Animals , Chlorides/metabolism , Colforsin/pharmacology , Electric Stimulation , Female , In Vitro Techniques , Intestinal Mucosa/drug effects , Intestinal Mucosa/innervation , Intestinal Mucosa/metabolism , Jejunum/innervation , Jejunum/metabolism , Male , Membrane Potentials/drug effects , Neurons/physiology , Sodium/metabolism , Swine , Tetrodotoxin/pharmacologyABSTRACT
The tetradecapeptide somatostatin-14 (SS-14) has been found to alter electrogenic ion transport in the rat, guinea pig and rabbit intestinal mucosa in vitro. In this study, the actions of SS-14 and related peptides on mucosal ion transport were investigated in the intestinal tract of the pig, a species whose digestive physiology is similar to man. The contraluminal- but not luminal-side administration of SS-14 (1-1000 nmol/l) to sheets of mucosa-submucosa obtained from different regions of the porcine small intestine and colon produced rapid, sustained decreases in short-circuit current (lsc), a measure of active ion transport, that were localized to segments of the distal jejunum. The magnitude of this peptide action was greater in tissues manifesting a serosapositive basal potential difference greater than 0 mV than in those displaying a spontaneous potential difference less than 0 mV. Under basal conditions, SS-14 produced a maximum decrease in distal jejunal lsc which was nearly twice that produced by its synthetic analog SMS 201,995 (octreotide); the two peptides inhibited lsc with similar potencies. SS-14 (10 nmol/l) increased the lumen-to-serosa transepithelial Cl flux and eliminated net residual flux. Mucosal lsc responses to SS-14 were absent in tissues bathed in HCO3-free media. Peptide actions were generally resistant to inhibitors of epithelial anion exchange, Na-proton exchange and NaCl cotransport. The adenylate cyclase activator forskolin (1 mumol/l) and the cyclic AMP analog 8-bromo-cyclic AMP (0.3 mmol/l) evoked net Cl secretion which was associated with rapid and sustained elevations in lsc.(ABSTRACT TRUNCATED AT 250 WORDS)
