Flemström Gunnar, Sjöblom Markus, Jedstedt Gunilla, Akerman Karl E O
Department of Neuroscience, Division of Physiology, Uppsala University, SE-751 23 Uppsala, Sweden.
Am J Physiol Gastrointest Liver Physiol. 2003 Dec;285(6):G1091-6. doi: 10.1152/ajpgi.00193.2003. Epub 2003 Jul 17.
Orexins are involved in the central nervous control of appetite and behavior, and in addition, they are present in endocrine cells and/or neurons in the intestine. The role of these peptides in peripheral regulation of intestinal secretion has not been investigated. We thus compared the effects of orexin A and some established secretagogues on duodenal HCO3- secretion in fed rats with effects in rats exposed to short (overnight) food deprivation. Rats were anesthetized with thiobarbiturate, a 12-mm segment of proximal duodenum with intact blood supply was cannulated in situ, and the alkaline secretion was titrated by pH stat. Secretagogues were supplied specifically to the duodenum by close intra-arterial infusion. Orexin A (60-600 pmol x kg(-1) x h(-1)) caused marked and dose-dependent stimulation of the duodenal secretion in fed animals but did not affect secretion in overnight food-deprived animals. Similarly, short fasting caused a 100-fold increase in the amount of the muscarinic agonist bethanechol (from 50 to 5,000 nmol x kg(-1) x h(-1)) required for stimulation of the secretion. In contrast, the secretory responses to VIP (50-1,000 pmol x kg(-1) x h(-1)) and melatonin (20-200 nmol x kg(-1) x h(-1)) were not affected. The appetite-regulating peptide orexin A is thus a stimulant of intestinal secretion, but the response to this peptide as well as the muscarinic agonist bethanechol is markedly dependent on previous intake of food. Overnight fasting is a standard experimental procedure in studies of gastrointestinal function and pathophysiology in humans and animals. Studies made on neuroendocrine control of intestinal secretion may require reevaluation with respect to feeding status.
食欲肽参与食欲和行为的中枢神经控制，此外，它们还存在于肠道的内分泌细胞和/或神经元中。这些肽在肠道分泌的外周调节中的作用尚未得到研究。因此，我们比较了食欲肽A和一些已确定的促分泌素对进食大鼠十二指肠HCO3-分泌的影响与对短期（过夜）禁食大鼠的影响。用硫代巴比妥酸盐麻醉大鼠，将一段12毫米长、血液供应完整的十二指肠近端原位插管，并用pH计滴定碱性分泌。促分泌素通过动脉内近距离输注专门供应给十二指肠。食欲肽A（60 - 600 pmol·kg-1·h-1）在进食动物中引起十二指肠分泌的显著且剂量依赖性刺激，但对过夜禁食动物的分泌没有影响。同样，短期禁食使刺激分泌所需的毒蕈碱激动剂氨甲酰甲胆碱的量增加了100倍（从50到5000 nmol·kg-1·h-1）。相比之下，对血管活性肠肽（50 - 1000 pmol·kg-1·h-1）和褪黑素（20 - 200 nmol·kg-1·h-1）的分泌反应不受影响。因此，调节食欲的肽食欲肽A是肠道分泌的刺激物，但对该肽以及毒蕈碱激动剂氨甲酰甲胆碱的反应明显取决于先前的食物摄入情况。过夜禁食是人类和动物胃肠道功能及病理生理学研究中的标准实验程序。关于肠道分泌的神经内分泌控制的研究可能需要根据进食状态进行重新评估。
