xenin-25 and xenopsin

Peptides related to the amphibian octapeptide xenopsin are present in various locations in mammalians, such as the gastrointestinal mucosa or brain tissue. In the gastrointestinal tract, xenopsin-related peptides induce partially neurogenic contractions of the colon in humans. In brain, however, their function is not known. Structural similarities of xenopsin-related peptides with neurotensin, a known modulator of ingestive behavior, suggest a possible role in feeding regulation. Therefore, we examined the effect of xenin, a recently identified xenopsin-related pentacosa peptide, on feeding behavior of fasted rats. Male Wistar rats (n=12) were intracerebroventricularly (i.c.v.) injected with either saline (10 microl) or xenin at 0.5, 1.5, 5 or 15 microg dissolved in an identical volume of 10 microl, respectively. In further experiments, xenin 15 microg/0.5 microl or 0.5 microl saline were injected into the lateral hypothalamus (LH). After injections, food intake (g), percentage of time spent with feeding (%) and prandial water intake (ml) were subsequently recorded for 2 h. After i.c.v. injection of 15 microg of xenin 1-h food intake was significantly reduced by 42% and 2-h food intake was diminished by 25%, respectively, compared to saline injection (p<0.01). This reduction of food intake was paralleled by a significant decrease of time spent with feeding by 41% (after 1 h) or 23% (after 2 h). The xenin-induced suppression of feeding behavior was dose-dependent. Thus, the minimal effective dose of xenin was 1.5 microg, while the dose of 0.5 microg was ineffective. Prandial water intake was significantly reduced only by the highest dose of xenin. Following injection of 15 microg of xenin into the lateral hypothalamus food intake was not different from control experiments. These data demonstrate a potent feeding suppressive action of xenin following intracerebroventricularly injection but not injection into the lateral hypothalamus suggesting a possible role of xenin in the central control of feeding termination and satiety.

Topics: Amino Acid Sequence; Animals; Eating; Fasting; Feeding Behavior; Gastrointestinal Hormones; Hypothalamus; Injections, Intraventricular; Male; Microinjections; Molecular Sequence Data; Neurotensin; Oligopeptides; Peptides; Rats; Rats, Wistar; Satiation; Sodium Chloride; Xenopus Proteins

One of the peptides previously discovered in amphibians is the octapeptide xenopsin. As immunohistochemistry has also indicated the presence of xenopsin immunoreactivity in man, we extracted in the present investigation xenopsin-immunoreactive material from human gastric mucosa and purified it to homogeneity with several high performance liquid chromatography (HPLC) reverse phase and ion exchange chromatographic steps. The eluates were monitored with a radioimmunoassay for amphibian xenopsin. Determination of the amino acid sequence revealed a 25-amino acid peptide having 6 C-terminal amino acids in common with amphibian xenopsin. The sequence of this peptide, termed xenin 25, is M-L-T-K-F-E-T-K-S-A-R-V-K-G-L-S-F-H-P-K-R-P-W-I-L. The peptide was custom-synthesized. Mass spectrometry of the synthetic and the extracted peptide revealed identical molecular mass. Purification of 250 ml of human postprandial plasma with Sep-Pak C18 cartridges, reverse phase HPLC, and ion exchange chromatography demonstrated circulating xenin immunoreactivity at a retention time identical to xenin 25. The amount of xenin immunoreactivity at the position of xenin 25 on C18-HPLC increased significantly after a meal. A radioimmunoassay utilizing antibodies to xenin 25 and a 125I-labeled analogue of xenin 25 was used to measure immunoreactive xenin in the plasma of 10 volunteers. There was a significant rise of xenin immunoreactivity in the plasma after a meal. Intravenous infusion of the synthetic peptide in dogs stimulated exocrine pancreatic secretion beginning at a dose of 4 pmol/kg/min. The maximal effect was seen with 64 pmol/kg/min. We have detected, therefore, a new peptide, xenin 25, in human gastric mucosa; we have provided evidence for the presence of this peptide in the human circulation, and have shown a rise of plasma xenin concentrations after a meal. This peptide stimulates exocrine pancreatic secretion. Its physiologic role deserves further investigation.

Topics: Amino Acid Sequence; Animals; Dogs; Gastric Mucosa; Gastrointestinal Hormones; Humans; Mass Spectrometry; Molecular Sequence Data; Neurotensin; Oligopeptides; Pancreatic Juice; Peptides; Secretory Rate; Sequence Alignment; Xenopus Proteins