Gylfe E, Hellman B
Mol Pharmacol. 1982 Nov;22(3):715-20.
Beta-Cell-rich pancreatic islets, neurohypophyses, and adrenal medullae were used for exploring whether hypoglycemic sulfonylureas exhibit Ca2+ ionophoretic properties. Exposure of these excitable organs to depolarizing concentrations of K+ resulted in stimulation both of 45Ca uptake and efflux. Although tolbutamide does not bind preferentially to pancreatic islets, this sulfonylurea was specific in stimulating the fluxes of 45Ca in these endocrine specimens. A chromaffin granule preparation was used for studies of both the net transport of Ca2+ with the metallochromic indicator arsenazo III and the proton concentration gradient (delta pH) with the fluorescent probe 9-aminoacridine. Even at high concentrations, tolbutamide and glibenclamide did not mediate Ca2+ -H+ exchange diffusion whether or not the granules were made permeable to protons by the addition of the protonophore carbonyl cyanide rho-trifluoromethoxyphenylhydrazone, nor did the sulfonylureas affect Ca2+ -H+ exchange diffusion induced by the addition of A-23187. The data indicate that the Ca2+ fluxes associated with sulfonylurea-stimulated insulin secretion do not result from the Ca2+ -ionophoretic properties of the drugs but rather reflect depolarization of the beta-cells.
富含β细胞的胰岛、神经垂体和肾上腺髓质被用于探究降糖磺脲类药物是否具有钙离子载体特性。将这些可兴奋器官暴露于去极化浓度的钾离子中会刺激45钙的摄取和流出。虽然甲苯磺丁脲不会优先结合胰岛，但这种磺脲类药物在刺激这些内分泌标本中的45钙通量方面具有特异性。嗜铬颗粒制剂用于研究用金属铬指示剂偶氮胂III对钙离子的净转运以及用荧光探针9-氨基吖啶对质子浓度梯度（ΔpH）的研究。即使在高浓度下，无论是否通过添加质子载体羰基氰化物间三氟甲氧基苯腙使颗粒对质子具有通透性，甲苯磺丁脲和格列本脲都不会介导钙离子-氢离子交换扩散，磺脲类药物也不会影响添加A-23187诱导的钙离子-氢离子交换扩散。数据表明，与磺脲类药物刺激胰岛素分泌相关的钙离子通量并非由药物的钙离子载体特性引起，而是反映了β细胞的去极化。
