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 o r brain tissue. In the gastrointestinal tract, xenopsin-related peptid es 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 in gestive behavior, suggest a possible role in feeding regulation. There fore, we examined the effect of xenin, a recently identified xenopsin- related pentacosa peptide, on feeding behavior of fasted rats. Male Wi star rats (n = 12) were intracerebroventricularly (i.c.v.) injected wi th either saline (10 mu l) or xenin at 0.5, 1.5, 5 or 15 mu g dissolve d in an identical volume of 10 mu l, respectively. In further experime nts, xenin 15 mu g/0.5 mu l or 0.5 mu l saline were injected into the lateral hypothalamus (LH). After injections, food intake (g), percenta ge of time spent with feeding (%) and prandial water intake (ml) were subsequently recorded for 2 h. After i.c.v. injection of 15 mu g of xe nin 1-h food intake was significantly reduced by 42% and 2-h food inta ke was diminished by 25%, respectively, compared to saline injection ( p < 0.01). This reduction of food intake was paralleled by a significa nt decrease of time spent with feeding by 41% (after 1 h) or 23% (afte r 2 h). The xenin-induced suppression of feeding behavior was dose-dep endent. Thus, the minimal effective dose of xenin was 1.5 mu g while t he dose of 0.5 mu g was ineffective. Prandial water intake was signifi cantly reduced only by the highest dose of xenin. Following injection of 15 mu g of xenin into the lateral hypothalamus food intake was not different from control experiments. These data demonstrate a potent fe eding 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. (C) 1998 Elsevier Science B.V. All rights reserved.