The adenylate cyclase-inhibiting bradykinin receptor in guinea pig ileum membranes exhibits an unique antagonist profile.
The purpose of the present study was to characterize more precisely an inhibitory, adenylate cyclase-coupled bradykinin receptor in guinea pig ileum membranes. Therefore, the effects of various well-known bradykinin B2 receptor antagonists were examined at the level of bradykinin-induced inhibition of ileal adenylate cyclase activity and compared with both their binding affinities and their potencies to antagonize ileal contraction evoked by bradykinin. A group of three highly potent antagonists was found to be able to antagonize both bradykinin-induced adenylate cyclase inhibition and smooth muscle contraction. Several other antagonists abolished the bradykinin-induced ileal contraction but did not influence its action on adenylate cyclase. The compound [D-Nal1, Thi5,8, D-Phe7]bradykinin which is known to inhibit the bradykinin-induced contraction in the rat uterus but not in the guinea pig ileum was found to be a weak but selective antagonist for the adenylate cyclase-coupled bradykinin receptor in guinea pig ileum. Altogether, in guinea pig ileum membranes the inhibitory, adenylate cyclase-coupled bradykinin B2 receptor with pM affinity towards bradykinin exhibits a unique antagonist profile and is distinguished from the excitatory bradykinin B2 receptor with nM affinity towards bradykinin.
Liebmann
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C
Institute of Biochemistry and Biophysics, Biological Faculty, Friedrich-Schiller-University, Jena, Germany.
Graness
A
A
Adomeit
A
A
Nawrath
S
S
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D001667:Binding, Competitive; D001920:Bradykinin / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects*; D008566:Membranes / Q000187:drug effects; D051381:Rats; D018002:Receptors, Bradykinin / Q000187:drug effects*; D014599:Uterus / Q000187:drug effects*
D018002:Receptors, Bradykinin; D000262:Adenylyl Cyclases; D001920:Bradykinin