Kinin B1and B2receptors in the mouse

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Abstract
A systematic study has been performed in various segments of the intestine and in the urinary bladder of the mouse to identify tissues that respond to kinins and possess B1and (or) B2receptors. The stomach was found to contain B1and B2functional sites that show pharmacological profiles compatible with B1and B2receptors, whereas the urinary bladder possesses only B2sites. Myotropic responses mediated by B1receptors show slow onset and reversibility compared with responses evoked by the activation of B2receptors. The order of potency of agonists is bradykinin (BK) ≥ [Hyp3]BK > [Aib7]BK on the B2of both the stomach and urinary bladder, while desArg9-BK is inactive. The order of potency of agonists on the B1receptor is [Lys]desArg9BK ≤ desArg9BK, while BK and the other B2agonists are inactive. B2antagonists of the first generation, such as DArg[Hyp3,DPhe7]BK, act as partial agonists and show 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 B1receptor, classical antagonists, such as [Leu8]desArg9BK and Lys[Leu8]desArg9BK, act as partial agonists. A modification of their structures has led to a new compound (R-715) that shows fairly high affinity (pA27.0) and little residual agonistic effect. This compound has been used for B1receptor characterization in the stomach. Residual agonistic activities of both B2and B1antagonists appear to be mediated by B2and B1receptors, respectively. Data presented in this paper provide the pharmacological basis for sensitive and selective preparations to be used for studying B1and B2receptors in the mouse.Key words: mouse, stomach, urinary bladder, bradykinin, B1and B2receptors, antagonists.