The function and the expression of two Bradykinin (B1, B2) receptor subtypes

• Published in: Japanese Journal of Pharmacology Vol. 71; no. suppl.1; p. 69
• Main Authors: Zenkoh, Junko, Aramori, Ichiro, Morikawa, Noriyuki, O'Donnell, Nuala, Nakamura, Kozo, Iwami, Morita, Kojo, Hitoshi, Notsu, Yoshitada
• Format: Journal Article
• Language: English; Japanese
• Published: The Japanese Pharmacological Society 1996
• ISSN: 0021-5198
• DOI: 10.1016/S0021-5198(19)36515-1

The two bradykinin receptors(B1, B2) have seven hydrophobic segments and share a sequence similarity with G protein-coupled receptors. We investigated the pharmacological properties of the two bradykinin receptors and the induction of B 1 mRNA in order to define their physiological functions. We have established the chinese hamster ovary (CHO) cell line stably expressing the human B1 and B2 receptors respectively. Then we examined the receptor-binding properties of some bradykinin analogs and the effects of bradykinin and des-Arg^10 -kallidin application on IPs formation in established cells. By displacement analysis using membrane preparations derived from established cells, B 1 receptor has shown to exhibit a rank order of binding affinities of des-Arg^10 -kallidin > kallidin > des-Arg^9 -bradykinin = des-Arg^9 [Leu^8 ]-bradykinin >> bradykinin, whereas a rank order of potency for the B 2 receptor has shown to be bradykinin = kallidin >> des-Arg^9 -bradykinin = des-Arg^9 [Leu^8 ]-bradykinin = des-Arg^10 -kallidin. The two bradykinin receptors have been shown to mediate the stimulation of PI hydrolysis through G protein by the effects of bradykinin and des-Arg^10 -kallidin application on IPs formation in cells expressing the B1 and B2 receptor respectively. The tissue distribution of B1 and B2 mRNA was investigated by northern blot analysis. B2 mRNA was widely distributed in human normal tissues. It was shown higher expression in brain, skeletal muscle, pancreas and especially in kidney. B 1 mRNA was detected only in kidney. The B1 mRNA was induced by the IL-1β in human embryonic fibroblast cells (IMR-90) and B1 mRNA level was increased by being cultured for 2hrs in medium containing IL- 1β. These results suggest that the functions of B1 and B2 receptors were divided by the difference of their tissue distribution and ligand specificities. It is possible that production of IPs stimulated by the interaction of ligands with bradykinin receptors activate certain enzymes related to inflammation. And it is indicated that B 1 mRNA was induced following release of inflammatory mediators and B 1 plays important role for inflammation.