Existence of three subtypes of bradykinin B2 receptors in guinea pig.
We describe the binding of [3H]bradykinin to homogenates of guinea pig brain, lung, and ileum. Analysis of [3H]bradykinin binding kinetics in guinea pig brain, lung, and ileum suggests the existence of two binding sites in each tissue. The finding of two binding sites for [3H]bradykinin in ileum, lung, and brain was further supported by Scatchard analysis of equilibrium binding in each tissue. [3H]Bradykinin binds to a high-affinity site in brain, lung, and ileum (KD = 70-200 pM), which constitutes approximately 20% of the bradykinin binding, and to a second, lower-affinity site (0.63-0.95 nM), which constitutes the remaining 80% of binding. Displacement studies with various bradykinin analogues led us to subdivide the high- and lower-affinity sites in each tissue and to suggest the existence of three subtypes of B2 receptors in the guinea pig, which we classify as B2a, B2b, and B2c. Binding of [3H]bradykinin is largely to a B2b receptor subtype, which constitutes the majority of binding in brain, lung, and ileum and represents the lower-affinity site in our binding studies. Receptor subtype B2c constitutes approximately 20% of binding sites in the brain and lung and is equivalent to the high-affinity site in brain and lung. We suggest that a third subtype of B2 receptor (high-affinity site in ileum), B2a, is found only in the ileum. All three subtypes of B2 receptors display a high affinity for bradykinin, whereas they show different affinities for various bradykinin analogues displaying agonist or antagonist activities.(ABSTRACT TRUNCATED AT 250 WORDS)
Seguin
L
L
Division of Molecular and Cellular Biology, Institut de Recherches Servier, Suresnes, France.
Widdowson
P S
PS
Giesen-Crouse
E
E
D000704:Analysis of Variance; D000818:Animals; D001920:Bradykinin / Q000378:metabolism; D001921:Brain / Q000648:ultrastructure; D001923:Brain Chemistry; D006168:Guinea Pigs; D007082:Ileum / Q000737:chemistry / Q000648:ultrastructure; D008168:Lung / Q000737:chemistry / Q000648:ultrastructure; D008297:Male; D011485:Protein Binding; D018002:Receptors, Bradykinin; D017981:Receptors, Neurotransmitter / Q000032:analysis / Q000737:chemistry* / Q000378:metabolism
D018002:Receptors, Bradykinin; D017981:Receptors, Neurotransmitter; D001920:Bradykinin