KININ B-1 AND B-2 RECEPTORS IN THE MOUSE

A systematic study has been performed in various segments of the intes tine and in the urinary bladder of the mouse to identify tissues that respond to kinins and possess B-1 and (or) B-2 receptors. The stomach was found to contain B-1 and B-2 functional sites that show pharmacolo gical profiles compatible with B-1 and B-2 receptors, whereas the urin ary bladder possesses only B-2 sites. Myotropic responses mediated by B-1 receptors show slow onset and reversibility compared with response s evoked by the activation of B-2 receptors. The order of potency of a gonists is bradykinin (BK) greater than or equal to [Hyp(3)]BK > [Aib( 7)]BK on the B-2 of both the stomach and urinary bladder, while desArg (9)-BK is inactive. The order of potency of agonists on the B-1 recept or is [Lys]desArg(9)BK less than or equal to desArg(9)BK, while BK and the other B-2 agonists are inactive. B-2 antagonists of the first gen eration, such as DArg[Hyp(3),DPhe(7)]BK, act as partial agonists and s how residual agonistic activities higher than 0.5, while HOE-140 shows high affinity and very little residual agonistic activity; WIN 64338 is almost inactive. On the B-1 receptor, classical antagonists, such a s [Leu(8)]desArg(9)BK and Lys[Leu(8)]desArg(9)BK, act as partial agoni sts. A modification of their structures has led to a new compound (R-7 15) that shows fairly high affinity (pA(2) 7.0) and little residual ag onistic effect. This compound has been used for B-1 receptor character ization in the stomach. Residual agonistic activities of both B-2 and B-1 antagonists appear to be mediated by B-2 and B-1 receptors, respec tively. Data presented in this paper provide the pharmacological basis for sensitive and selective preparations to be used for studying B-1 and B-2 receptors in the mouse.