engleski

3H- angiotensin II binding to rat isolated glomeruli - the effects of valsartan, angiotensin II, angiotensin I and lisinopril

In an attempt to characterise, optimise and standardise conditions for 3H-angiotensin II binding to AT1 angiotensin receptors from isolated rat glomeruli, the effect of angiotensin II, angiotensin I, lisinopril and valsartan were investigated. In concentrations ranging from 100 pM to 100 nM, angiotensin II displaced 3H-angiotensin II binding to isolated rat glomeruli with highest affinity (IC50 = 11.8 nM). Angiotensin I also inhibited 3H-angiotensin II binding to isolated rat glomeruli, but with two orders of magnitude weaker affinity as compared to angiotensin II. Furthermore, lisinopril, an angiotensin convertase enzyme inhibitor, enhanced 3H-angiotensin II binding to isolated rat glomeruli, in concentration independent manner. Finally, valsartan, high specific and selective competitive antagonist at AT1 angiotensin receptors showed quite unusual binding interaction with angiotensin receptors from isolated rat glomeruli. In nanomolar concentrations, valsartan enhanced 3H-angiotensin II binding. Besides, valsartan changed the shape of binding curve for angiotensin II from classical, displacement curve (angiotesin II alone) into biphasic curve (enhancement of 3H-angiotensin II binding with low nanomolar concentrations, followed by displacement of 3H-angiotensin II binding with high nanomolar concentrations). In conclusion, the results presented here, indicate an unknown, non-competitive interaction of valsartan with angiotensin receptors from isolated rat glomeruli labelled with 3H-angiotensin II.

3H-angiotensin II; isolated glomeruli; drugs

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