Ismail N A, Shaheen A A, el-Sawalhi M M, Megahed Y M
Biochemistry Department, Faculty of Pharmacy, Cario University, Egypt.
Arzneimittelforschung. 1995 Aug;45(8):865-8.
The present work was performed to study the effect of two calcium channel antagonists, namely verapamil (CAS 52-53-9) and nifedipine (CAS 21829-25-4) in modifying the inhibitory influence of adenosine on insulin secretion from isolated rat pancreatic islets. The combined effect of adenosine and these agents on serum insulin and glucose levels in vivo was also investigated. Both verapamil and nifedipine at 100 mumol/l and 1 mumol/l, respectively, produced a significant inhibition of glucose-stimulated insulin secretion from pancreatic islets. Combination of these agents with adenosine 10 mumol/l did not modify the inhibitory effect of adenosine on insulin secretion. Verapamil (21.6 mg/kg b.wt.) and nifedipine (5.4 mg/kg b.wt.) intraperitoneally injected prior to glucose loading produced a significant increase in serum glucose with an accompanied decrease in serum insulin levels. Concurrent administration of verapamil with adenosine neither affected the hyperglycaemic nor the hypoinsulinaemic effects of adenosine, whereas combined administration of nifedipine and adenosine decreased the hyperglycaemic effect of adenosine but not its hypoinsulinaemic effect. These results may indicate that these calcium channel antagonists do not interact with adenosine receptors which mediate its inhibitory effect on insulin secretion.
开展本研究旨在探讨两种钙通道拮抗剂，即维拉帕米（化学物质登记号52 - 53 - 9）和硝苯地平（化学物质登记号21829 - 25 - 4）对腺苷抑制离体大鼠胰岛胰岛素分泌的影响。还研究了腺苷与这些药物对体内血清胰岛素和葡萄糖水平的联合作用。维拉帕米和硝苯地平分别在100 μmol/l和1 μmol/l浓度时，均对胰岛葡萄糖刺激的胰岛素分泌产生显著抑制作用。这些药物与10 μmol/l腺苷联合使用并未改变腺苷对胰岛素分泌的抑制作用。在葡萄糖负荷前腹腔注射维拉帕米（21.6 mg/kg体重）和硝苯地平（5.4 mg/kg体重）可使血清葡萄糖显著升高，同时血清胰岛素水平降低。维拉帕米与腺苷同时给药既不影响腺苷的高血糖作用，也不影响其低血糖素作用，而硝苯地平和腺苷联合给药则降低了腺苷的高血糖作用，但不影响其低血糖素作用。这些结果可能表明，这些钙通道拮抗剂不与介导其对胰岛素分泌抑制作用的腺苷受体相互作用。
