Bengtsson M W, Jedstedt G, Flemström G
Department of Neuroscience, Division of Physiology, Uppsala University, Uppsala, Sweden.
Acta Physiol (Oxf). 2007 Dec;191(4):309-17. doi: 10.1111/j.1748-1716.2007.01759.x.
Uroguanylin and guanylin are endogenous ligands for guanylate cyclase C, an upstream regulator of the cystic fibrosis transmembrane resistance (CFTR) anion channel, and both peptides increase intestinal anion export in vitro. We have compared the effects of close intra-arterial and luminal administration of uroguanylin and guanylin on duodenal bicarbonate secretion in vivo and studied the interactions with melatonin and cholinergic stimulation.
Lewis x Dark Agouti rats were anaesthetized and a segment of the proximal duodenum with intact blood supply was cannulated in situ. Mucosal bicarbonate secretion (pH stat) was continuously recorded and peptides were infused intra-arterially or added to the luminal perfusate.
Intra-arterial (50-1000 pmol kg(-1) h(-1)) as well as luminal administration (50-500 nmol L(-1)) of guanylin or uroguanylin caused dose-dependent increases in the duodenal secretion. Luminal administration induced more rapidly appearing rises in secretion and the two peptides induced secretory responses of similar shape and magnitude. The melatonin MT(2)-selective antagonist luzindole (600 nmol kg(-1)) significantly depressed the response to intra-arterial guanylins but did not affect secretion induced by luminal guanylins. Similarly, the muscarinic antagonist atropine (0.75 micromol kg(-1) followed by 0.15 micromol kg(-1) h(-1)) abolished the response to intra-arterial uroguanylin but caused only slight suppression of the response to luminal uroguanylin.
Intra-arterial as well as luminal uroguanylin and guanylin are potent stimuli of duodenal mucosal bicarbonate secretion in vivo. The response to luminal guanylins reflects an action at apical receptors. Stimulation by parenteral guanylins, in contrast, is under cholinergic influence and interacts with melatonin produced by mucosal enteroendocrine cells.
尿鸟苷素和鸟苷素是鸟苷酸环化酶C的内源性配体，鸟苷酸环化酶C是囊性纤维化跨膜传导调节因子（CFTR）阴离子通道的上游调节因子，两种肽均可在体外增加肠道阴离子分泌。我们比较了尿鸟苷素和鸟苷素经动脉内近距离给药和腔内给药对体内十二指肠碳酸氢盐分泌的影响，并研究了它们与褪黑素和胆碱能刺激的相互作用。
将Lewis×Dark Agouti大鼠麻醉，在原位将一段血供完整的十二指肠近端插管。连续记录黏膜碳酸氢盐分泌（pH稳态），肽经动脉内注入或添加到腔内灌流液中。
动脉内（50 - 1000 pmol kg⁻¹ h⁻¹）以及腔内给予（50 - 500 nmol L⁻¹）鸟苷素或尿鸟苷素均可引起十二指肠分泌呈剂量依赖性增加。腔内给药引起的分泌增加出现更快，两种肽引起的分泌反应形状和幅度相似。褪黑素MT₂选择性拮抗剂鲁辛朵（600 nmol kg⁻¹）显著抑制对动脉内鸟苷素的反应，但不影响腔内鸟苷素诱导的分泌。同样，毒蕈碱拮抗剂阿托品（0.75 μmol kg⁻¹，随后0.15 μmol kg⁻¹ h⁻¹）消除了对动脉内尿鸟苷素的反应，但仅轻微抑制了对腔内尿鸟苷素的反应。
动脉内以及腔内给予尿鸟苷素和鸟苷素均是体内十二指肠黏膜碳酸氢盐分泌的有效刺激物。对腔内鸟苷素的反应反映了其对顶端受体的作用。相比之下，胃肠外给予鸟苷素的刺激受胆碱能影响，并与黏膜肠内分泌细胞产生的褪黑素相互作用。
