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 B1 and (or) B2 receptors. The stomach was found to contain B1 and B2 functional sites that show pharmacological profiles compatible with B1 and B2 receptors, whereas the urinary bladder possesses only B2 sites. Myotropic responses mediated by B1 receptors show slow onset and reversibility compared with responses evoked by the activation of B2 receptors. The order of potency of agonists is bradykinin (BK) > or = [Hyp3]BK > [Aib7]BK on the B2 of both the stomach and urinary bladder, while desArg9-BK is inactive. The order of potency of agonists on the B1 receptor is [Lys]desArg9BK < or = desArg9BK, while BK and the other B2 agonists are inactive. B2 antagonists 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 B1 receptor, 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 (pA2 7.0) and little residual agonistic effect. This compound has been used for B1 receptor characterization in the stomach. Residual agonistic activities of both B2 and B1 antagonists appear to be mediated by B2 and B1 receptors, respectively. Data presented in this paper provide the pharmacological basis for sensitive and selective preparations to be used for studying B1 and B2 receptors in the mouse.
journal_name
Can J Physiol Pharmacoljournal_title
Canadian journal of physiology and pharmacologyauthors
Allogho SN,Gobeil F,Pheng LH,Nguyen-Le XK,Neugebauer W,Regoli Ddoi
10.1139/y95-240subject
Has Abstractpub_date
1995-12-01 00:00:00pages
1759-64issue
12eissn
0008-4212issn
1205-7541journal_volume
73pub_type
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