Moro F, Levenez F, Nemoz-Gaillard E, Pellissier S, Plaisancie P, Cuber J C
INSERM, U-45, Hôpital Edouard Herriot, Lyon, France.
Endocrinology. 2000 Jul;141(7):2594-9. doi: 10.1210/endo.141.7.7574.
The intestinal peptide guanylin regulates the electrolyte/water transport in the intestinal epithelium. The aim of the present study was to investigate the mechanisms that modulate its secretion in the isolated vascularly perfused rat colon by using a specific guanylin RIA. Intraarterial infusion of bethanechol (10(-4) M) or bombesin (10(-7) M) elicited a significant 6-fold increase in the release of guanylin immunoreactivity (G-IR) in the lumen. Bombesin-stimulated G-IR secretion was strongly reduced by tetrodotoxin, whereas atropine had no effect. VIP (10(-7) M) induced a moderate release of G-IR, whereas substance P, calcitonin gene-related peptide, peptide YY, somatostatin, and neurotensin were without effect. Dimethyl-PGE2 (1.4 x 10(-5) M) or interleukin-1beta (2.5 x 10(-10) M) induced a 3-fold increase in G-IR in the lumen, whereas the degranulator compound bromolasalocid did not stimulate guanylin secretion. Forskolin (10(-5) M) or sodium nitroprusside (10(-4)-10(-3) M) induced a significant release of G-IR. In contrast, PMA (10(-7) M) or ionophore A23187 (10(-6) M) did not modify basal secretion of G-IR. Upon stimulation of guanylin release with bombesin or bethanechol, an increase in G-IR in the portal effluent was also detected. The release of G-IR in the portal effluent was 40-fold lower than that of G-IR into the luminal perfusate. Additionally, analysis with gel chromatography revealed that the immunoreactive material released in the lumen or in the portal effluent coeluted with the 15-amino acid peptide originally isolated from rat intestine. In conclusion, the present data suggest that the enteric nervous system and immune cells may modulate guanylin release from the rat colon. The release of guanylin in the lumen and portal effluent suggests that this peptide may exert both luminal/paracrine and hormonal effects.
肠肽鸟苷素调节肠道上皮中的电解质/水转运。本研究的目的是通过使用特异性鸟苷素放射免疫分析法（RIA），研究在离体血管灌注大鼠结肠中调节其分泌的机制。动脉内注入氨甲酰甲胆碱（10⁻⁴ M）或蛙皮素（10⁻⁷ M）可使肠腔中鸟苷素免疫反应性（G-IR）的释放显著增加6倍。河豚毒素可强烈降低蛙皮素刺激的G-IR分泌，而阿托品则无作用。血管活性肠肽（VIP，10⁻⁷ M）诱导G-IR适度释放，而P物质、降钙素基因相关肽、肽YY、生长抑素和神经降压素则无作用。二甲基前列腺素E2（1.4×10⁻⁵ M）或白细胞介素-1β（2.5×10⁻¹⁰ M）可使肠腔中G-IR增加3倍，而脱颗粒剂化合物溴拉沙西啶则不刺激鸟苷素分泌。福斯高林（10⁻⁵ M）或硝普钠（10⁻⁴ - 10⁻³ M）可诱导G-IR显著释放。相反，佛波酯（PMA，10⁻⁷ M）或离子载体A23187（10⁻⁶ M）不改变G-IR的基础分泌。在用蛙皮素或氨甲酰甲胆碱刺激鸟苷素释放后，门静脉流出液中的G-IR也增加。门静脉流出液中G-IR的释放比肠腔灌注液中的G-IR低40倍。此外，凝胶色谱分析显示，在肠腔或门静脉流出液中释放的免疫反应性物质与最初从大鼠肠道分离的15个氨基酸的肽共洗脱。总之，目前的数据表明，肠神经系统和免疫细胞可能调节大鼠结肠中鸟苷素的释放。肠腔和门静脉流出液中鸟苷素的释放表明，该肽可能发挥腔内/旁分泌和激素作用。
