Article date: January 1995
By: D. Pruneau, A. Duvoid, J.M. Luccarini, P. Bélichard, J.C. Bonnafous, in Volume 114, Issue 1, pages 115-118
Agonists and antagonists of kinin B1 and B2 receptors were evaluated in vitro for their effects against angiotensin II (AII)‐induced contractile responses in the rabbit aorta and for their binding properties to angiotensin AT1 and AT2 receptors from purified membrane of rat liver and lamb uterus respectively.
In aortic rings, the kinin B1 receptor antagonist, des‐Arg9‐[Leu8]bradykinin (BK) (3–100 μm) caused a concentration‐dependent decrease in sensitivity and a depression of the maximum response to AII. Des‐Arg10‐[Leu9]kallidin (KD), des‐Arg9‐BK, des‐Arg10‐KD, BK or KD at 3 μm had no effect against All‐induced contractions.
Des‐Arg9‐[Leu8]BK (3 or 100 μm) did not affect contractions of aortic rings to histamine, potassium chloride, endothelin‐1, 5‐hydroxytryptamine, noradrenaline and the thromboxane A2‐mimetic, U46619.
Des‐Arg9‐[Leu8]BK displaced [125I]‐Sar1‐AII binding to the AT1 subtype in rat liver membranes with a Ki value of 1.1 ± 0.4 μm. Values of Ki for des‐Arg9‐BK and KD were 45 ± 13 μm and 25 ± 22 μm, respectively. The other kinin derivatives des‐Arg10‐KD, BK and des‐Arg10‐[Leu9]KD at concentrations up to 100 μm did not bind to the AT1 receptor.
All the kinin derivatives except BK bound to AT2 receptors in lamb uterus membranes. Values of Ki for des‐Arg9‐[Leu8]BK, des‐Arg10‐[Leu9]KD, des‐Arg9‐BK, des‐Arg10‐KD and KD were 0.3 ± 0.1, 0.7 ± 0.1, 1.2 ± 0.3, 1.5 ± 0.3 and 7.0 ± 1.6 μm, respectively.
In conclusion, des‐Arg9‐[Leu8]BK is an insurmountable antagonist of All‐induced contractions in the rabbit aorta and also binds with a relatively high affinity to AT1 and AT2 receptors in isolated membrane fractions. These additional properties of des‐Arg9‐[Leu8]BK should be considered when it is used as an antagonist to characterize kinin B1 receptors.
Agonists and antagonists of kinin B1 and B2 receptors were evaluated in vitro for their effects against angiotensin II (AII)‐induced contractile responses in the rabbit aorta and for their binding properties to angiotensin AT1 and AT2 receptors from purified membrane of rat liver and lamb uterus respectively.
In aortic rings, the kinin B1 receptor antagonist, des‐Arg9‐[Leu8]bradykinin (BK) (3–100 μm) caused a concentration‐dependent decrease in sensitivity and a depression of the maximum response to AII. Des‐Arg10‐[Leu9]kallidin (KD), des‐Arg9‐BK, des‐Arg10‐KD, BK or KD at 3 μm had no effect against All‐induced contractions.
Des‐Arg9‐[Leu8]BK (3 or 100 μm) did not affect contractions of aortic rings to histamine, potassium chloride, endothelin‐1, 5‐hydroxytryptamine, noradrenaline and the thromboxane A2‐mimetic, U46619.
Des‐Arg9‐[Leu8]BK displaced [125I]‐Sar1‐AII binding to the AT1 subtype in rat liver membranes with a Ki value of 1.1 ± 0.4 μm. Values of Ki for des‐Arg9‐BK and KD were 45 ± 13 μm and 25 ± 22 μm, respectively. The other kinin derivatives des‐Arg10‐KD, BK and des‐Arg10‐[Leu9]KD at concentrations up to 100 μm did not bind to the AT1 receptor.
All the kinin derivatives except BK bound to AT2 receptors in lamb uterus membranes. Values of Ki for des‐Arg9‐[Leu8]BK, des‐Arg10‐[Leu9]KD, des‐Arg9‐BK, des‐Arg10‐KD and KD were 0.3 ± 0.1, 0.7 ± 0.1, 1.2 ± 0.3, 1.5 ± 0.3 and 7.0 ± 1.6 μm, respectively.
In conclusion, des‐Arg9‐[Leu8]BK is an insurmountable antagonist of All‐induced contractions in the rabbit aorta and also binds with a relatively high affinity to AT1 and AT2 receptors in isolated membrane fractions. These additional properties of des‐Arg9‐[Leu8]BK should be considered when it is used as an antagonist to characterize kinin B1 receptors.
DOI: 10.1111/j.1476-5381.1995.tb14914.x
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