Elsevier

Neuropharmacology

Volume 34, Issue 1, January 1995, Pages 81-88
Neuropharmacology

General paper
Bradykinin modulation of α2-Adrenoceptors in the nucleus tractus solitarii of the rat. An in vitro autoradiographical study

https://doi.org/10.1016/0028-3908(94)00131-BGet rights and content

Abstract

The existence of an interaction between bradykinin (Bk) receptors and the α2-adrenoceptors were evaluated by means of quantitative receptor autoradiography in the nucleus tractus solitarii (NTS) of the rat. In competition experiments using l-noradrenaline (0.1 nM to 10 μM) against [3H]p-aminoclonidine ([3H]PAC) (10 nM) it was observed that Bk produced an increase in the IC50 value of l-noradrenaline in a concentration response manner, which reached a maximum of about 100% with 10 nM of the peptide associated with a small decrease in the B0 value (15%). In saturation experiments Bk promoted a significant increase in the KD value of [3H]PAC (60%) and a decrease in the Bmax value (36%). The specific Bk B2 receptor antagonist HOE-140 fully counteracted the effect of Bk on the α2-adrenoceptors as analyzed by the competition experiments. Furthermore, des-Arg9-Bk, a Bk analog which exhibits selective agonist activity to the Bk B1 receptor subtype did not produce any effect on the α2-adrenoceptors, suggesting that the Bk B2 receptor subtype may be mediating the Bk action on the α2-adrenoceptors in the NTS. The effect of Bk (10 nM) was analyzed together with GTP (0.1 mM) in competition experiments and no change in the ability of l-noradrenaline to compete for [3H]PAC binding sites was observed in the presence of GTP, suggesting that the receptor interaction between the Bk B2 receptors and the α2-adrenoceptors may be a G-protein dependent mechanism. The Bk-induced decrease in the affinity of l-noradrenaline for [3H]PAC binding sites suggest the existence of an antagonistic Bk B2 receptor/α2-adrenoceptor interaction which may be of relevance for the physiological actions of Bk in the NTS.

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