French J F, Riera L C, Mullins U L, Sarmiento J G
Bristol-Myers Squibb Pharmaceutical Research Institute, Cardiovascular Pharmacology, Wallingford, CT 06492.
Eur J Pharmacol. 1991 May 25;207(1):23-8. doi: 10.1016/s0922-4106(05)80033-1.
The existence of a single or of multiple populations of glibenclamide binding sites is a subject of controversy. In the present study, radioligand binding techniques were employed to determine whether multiple populations of [3H]glibenclamide binding sites exist in pancreatic tumor (insulinoma) cells. Additional studies were performed to further characterize the binding of [3H]glibenclamide to insulinoma and cardiac membranes. [3H]Glibenclamide bound to high (0.1 nM) and low (240 nM) affinity binding sites in insulinoma membranes. The physiological relevance of multiple populations of sites is unknown. The binding of glibenclamide to insulinoma and cardiac membranes was altered by guanine nucleotides and not adenine nucleotides. This suggests glibenclamide binding can be modulated by G-proteins. Glibenclamide binding was also modulated by divalent cations. The divalent cations, Ca2+ and Zn2+, stimulated specific glibenclamide binding to cardiac and insulinoma membranes, while Mg2+ and Mn2+ enhanced cardiac binding only. Moreover, the lowering of pH from 7.4 to 6.5 was found to enhance specific glibenclamide binding. Interestingly, the magnitude of this effect was much larger in cardiac membranes. The specific nature of the regulation of glibenclamide binding by guanine nucleotides, divalent cations and pH remains to be explored.
格列本脲结合位点是单一群体还是多个群体存在一直存在争议。在本研究中，采用放射性配体结合技术来确定胰腺肿瘤（胰岛素瘤）细胞中是否存在多个[3H]格列本脲结合位点群体。还进行了其他研究以进一步表征[3H]格列本脲与胰岛素瘤和心脏膜的结合。[3H]格列本脲与胰岛素瘤膜中的高亲和力（0.1 nM）和低亲和力（240 nM）结合位点结合。多个位点群体的生理相关性尚不清楚。格列本脲与胰岛素瘤和心脏膜的结合受鸟嘌呤核苷酸而非腺嘌呤核苷酸的影响。这表明格列本脲的结合可被G蛋白调节。格列本脲的结合也受二价阳离子调节。二价阳离子Ca2+和Zn2+刺激格列本脲与心脏和胰岛素瘤膜的特异性结合，而Mg2+和Mn2+仅增强心脏结合。此外，发现pH从7.4降至6.5会增强格列本脲的特异性结合。有趣的是，这种效应在心脏膜中的幅度要大得多。鸟嘌呤核苷酸、二价阳离子和pH对格列本脲结合的调节的具体性质仍有待探索。
