TY - JOUR
T1 - Neurohormonal regulation of ion transport in the porcine distal jejunum. Actions of neurotensin and its natural homologs
AU - Brown, David R
AU - Treder, B. G.
PY - 1989
Y1 - 1989
N2 - The tridecapeptide neurotensin (NT) is present at high concentrations within the mammalian gut, although its physiological function is undefined. In this study, the actions of NT and structurally related peptides neuromedin N (NM-N) and xenopsin were characterized on ion transport in the porcine distal jejunal mucosa in vitro. The serosal-side administration of these peptides elicited rapid changes in transmural potential difference and short-circuit current (Isc) which were greater in mesenteric than in antimesenteric segments. NT-induced elevations in Isc were dependend upon external permeant anions and were associated with net Cl transport in both segments. In mesenteric segments, NT and its homologs increased Isc with the order of potency: NT > NM-N > xenopsin. NT produced tachyphylaxis to its own actions and to those of NM-N; NM-N was ineffective in producing tachyphylaxis. Isc elevations produced by NT were inhibited by the neuronal conduction blocker tetrodotoxin (0.1 μM) or the Ca++-channel blocker dl-verapamil (100 μM) and reduced in Ca++-free media. Antagonists to the enteric transmitters acetylcholine, ATP, 5-hydroxytryptamine, substance P and histamine did not alter Isc responses of mesenteric segments to NT. Serosal administration of vasoactive intestinal peptide (10 nM) did not resemble the effects of NT. The magnitude of Isc responses to these agonists was smaller in antimesenteric segments. These results indicate that NT-related peptides present in mucosal endocrine cells or nerves of the porcine jejunum may modulate Cl transport through mechanisms that involve the Ca++-dependent release of unknown enteric neurotransmitters. Moreover, there appear to exist within the distal jejunum circumferential differences in mucosal responses to NT and other neurohumoral factors.
AB - The tridecapeptide neurotensin (NT) is present at high concentrations within the mammalian gut, although its physiological function is undefined. In this study, the actions of NT and structurally related peptides neuromedin N (NM-N) and xenopsin were characterized on ion transport in the porcine distal jejunal mucosa in vitro. The serosal-side administration of these peptides elicited rapid changes in transmural potential difference and short-circuit current (Isc) which were greater in mesenteric than in antimesenteric segments. NT-induced elevations in Isc were dependend upon external permeant anions and were associated with net Cl transport in both segments. In mesenteric segments, NT and its homologs increased Isc with the order of potency: NT > NM-N > xenopsin. NT produced tachyphylaxis to its own actions and to those of NM-N; NM-N was ineffective in producing tachyphylaxis. Isc elevations produced by NT were inhibited by the neuronal conduction blocker tetrodotoxin (0.1 μM) or the Ca++-channel blocker dl-verapamil (100 μM) and reduced in Ca++-free media. Antagonists to the enteric transmitters acetylcholine, ATP, 5-hydroxytryptamine, substance P and histamine did not alter Isc responses of mesenteric segments to NT. Serosal administration of vasoactive intestinal peptide (10 nM) did not resemble the effects of NT. The magnitude of Isc responses to these agonists was smaller in antimesenteric segments. These results indicate that NT-related peptides present in mucosal endocrine cells or nerves of the porcine jejunum may modulate Cl transport through mechanisms that involve the Ca++-dependent release of unknown enteric neurotransmitters. Moreover, there appear to exist within the distal jejunum circumferential differences in mucosal responses to NT and other neurohumoral factors.
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M3 - Article
C2 - 2468765
AN - SCOPUS:0024594168
SN - 0022-3565
VL - 249
SP - 348
EP - 357
JO - Journal of Pharmacology and Experimental Therapeutics
JF - Journal of Pharmacology and Experimental Therapeutics
IS - 1
ER -