Xenin--a novel suppressor of food intake in rats.
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.
Department of Internal Medicine II, Technical University of Munich, Munich, Germany.
C
C
Alexiou
J P
JP
Zimmermann
R R
RR
Schick
V
V
Schusdziarra
D000595:Amino Acid Sequence; D000818:Animals; D004435:Eating / Q000187:drug effects*; D005215:Fasting; D005247:Feeding Behavior / Q000187:drug effects*; D005768:Gastrointestinal Hormones / Q000737:chemistry / Q000494:pharmacology*; D007031:Hypothalamus / Q000187:drug effects / Q000502:physiology; D007276:Injections, Intraventricular; D008297:Male; D008845:Microinjections; D008969:Molecular Sequence Data; D009496:Neurotensin / Q000737:chemistry; D009842:Oligopeptides / Q000737:chemistry; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012527:Satiation / Q000187:drug effects; D012965:Sodium Chloride / Q000494:pharmacology; D029867:Xenopus Proteins
D005768:Gastrointestinal Hormones; D009842:Oligopeptides; D010455:Peptides; D029867:Xenopus Proteins; C077659:xenin 25; D009496:Neurotensin; D012965:Sodium Chloride; C016832:xenopsin