Alexiou C, Zimmermann J P, Schick R R, Schusdziarra V
Department of Internal Medicine II, Technical University of Munich, Munich, Germany.
Brain Res. 1998 Aug 3;800(2):294-9. doi: 10.1016/s0006-8993(98)00535-6.
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.
与两栖类八肽爪蟾肽相关的肽存在于哺乳动物的多个部位，如胃肠道黏膜或脑组织。在胃肠道中，与爪蟾肽相关的肽可诱导人类结肠发生部分神经源性收缩。然而，在大脑中，它们的功能尚不清楚。与神经降压素（一种已知的摄食行为调节剂）结构相似的与爪蟾肽相关的肽提示其在进食调节中可能发挥作用。因此，我们研究了最近鉴定出的与爪蟾肽相关的二十五肽爪蟾素对禁食大鼠进食行为的影响。雄性Wistar大鼠（n = 12）分别经脑室内（i.c.v.）注射10微升生理盐水或分别溶解于相同体积10微升中的0.5、1.5、5或15微克爪蟾素。在进一步的实验中，将15微克/0.5微升的爪蟾素或0.5微升生理盐水注入外侧下丘脑（LH）。注射后，随后记录2小时内的食物摄入量（克）、进食时间百分比（%）和餐时饮水量（毫升）。与注射生理盐水相比，经脑室内注射15微克爪蟾素后，1小时食物摄入量显著减少42%，2小时食物摄入量减少25%（p<0.01）。食物摄入量的减少伴随着进食时间显著减少41%（1小时后）或23%（2小时后）。爪蟾素诱导的进食行为抑制呈剂量依赖性。因此，爪蟾素的最小有效剂量为1.5微克，而0.5微克的剂量无效。仅最高剂量的爪蟾素能显著减少餐时饮水量。将15微克爪蟾素注入外侧下丘脑后，食物摄入量与对照实验无差异。这些数据表明，脑室内注射爪蟾素后具有强大的进食抑制作用，但注入外侧下丘脑则无此作用，提示爪蟾素在进食终止和饱腹感的中枢控制中可能发挥作用。
