Effects of various protease inhibitors on the stability and permeability of [D-Ala2,D-Leu5]enkephalin in the rat intestine: comparison with leucine enkephalin.
Effects of various protease inhibitors on the stability and permeability of [D-Ala2,D-Leu5]enkephalin in the rat intestine: comparison with leucine enkephalin.
复制标题
各种蛋白酶抑制剂对大鼠肠道内[D-Ala2,D-Leu5]脑啡肽稳定性和通透性的影响：与亮氨酸脑啡肽的比较。
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发表时间：
1998
期刊：
影响因子：
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通讯作者：
Akira Yamamoto
中科院分区：
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作者：
T. Uchiyama;A. Kotani;Takeshi Kishida;H. Tatsumi;Aya Okamoto;Takuya Fujita;M. Murakami;S. Muranishi;Akira Yamamoto
研究了不同蛋白酶抑制剂对亮氨酸脑啡肽（Leu-Enk）和[D-Ala 2，D-Leu 5]脑啡肽（DADLE）稳定性的影响，并在体外Ussing小室中考察了这些肽的渗透性。选择了巯甲丙脯酸、噻奥芬、杆菌肽、贝他丁、嘌呤霉素、阿马司他丁和甘胆酸钠（Na-GC）作为蛋白酶抑制剂。Leu-Enk和DADLE的稳定性存在地区差异，其稳定性顺序为结肠>十二指肠>回肠>空肠。Na-GC，amastatin，和嘌呤霉素是有效的蛋白酶抑制剂，用于改善这些肽的稳定性，虽然卡托普利和thiorphan没有改善Leu-Enk的稳定性。在转运研究中，Leu-Enk在不存在蛋白酶抑制剂的情况下不穿过肠膜，但在Na-GC存在下其转运得到改善。此外，Na-GC，amastatin和嘌呤霉素提高DADLE在空肠和结肠中的渗透性，而DADLE的渗透性没有通过添加巯甲丙脯酸，thiorphan和bestatin得到改善。此外，6-羧基荧光素，吸收性差，稳定的化合物，也提高了在钠-GC和杆菌肽的存在下，在10 mM的浓度。这些研究结果表明，amastatin，嘌呤霉素，和钠-GC在0.5 mM的浓度可能会增加DADLE的渗透性，由于提高了DADLE在供体部位的稳定性。然而，钠GC和杆菌肽在10 mM的浓度有吸收增强活动，这可能也与增加DADLE通过肠膜的渗透性。
The effects of various protease inhibitors on the stability of leucine enkephalin (Leu-Enk) and [D-Ala2,D-Leu5] enkephalin (DADLE) were investigated, and the permeability of these peptides was also examined in an in vitro Ussing chamber. Captopril, thiorphan, bacitracin, bestatin, puromycin, amastatin, and sodium glycocholate (Na-GC) were chosen as protease inhibitors. Regional differences in the stability of Leu-Enk and DADLE were observed, and the rank order of the stability of these peptides was colon > duodenum > ileum > jejunum. Na-GC, amastatin, and puromycin were effective protease inhibitors for improving the stability of these peptides, although captopril and thiorphan did not improve the stability of Leu-Enk. In the transport studies, Leu-Enk did not cross the intestinal membrane in the absence of protease inhibitors, but its transport was improved in the presence of Na-GC. In addition, Na-GC, amastatin, and puromycin improved the permeability of DADLE in both jejunum and colon, while the permeability of DADLE was not improved by the addition of captopril, thiorphan, and bestatin. Furthermore, the permeability of 6-carboxyfluorescein, a poorly absorbable and stable compound, was also improved in the presence of Na-GC and bacitracin at a concentration of 10 mM. These findings indicated that amastatin, puromycin, and Na-GC at a concentration of 0.5 mM might increase the permeability of DADLE due to the improved stability of DADLE in the donor site. However, Na-GC and bacitracin at a concentration of 10 mM had absorption-enhancing activities which might be also related to the enhanced permeability of DADLE across the intestinal membrane.