Fior D R, Fuxe K
Karolinska Institute, Department of Neuroscience, Stockholm, Sweden.
Neuropharmacology. 1995 Jan;34(1):81-8. doi: 10.1016/0028-3908(94)00131-b.
The existence of an interaction between bradykinin (Bk) receptors and the alpha 2-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 microM) 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 alpha 2-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 alpha 2-adrenoceptors, suggesting that the Bk B2 receptor subtype may be mediating the Bk action on the alpha 2-adrenoceptors in the NTS. The effect of Bk (10 nM) was analyzed together with GTP (0.1 nM) 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 alpha 2-adrenoceptors may be a G-protein dependent mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)
