Overexpression of kinin B1 receptors induces hypertensive response to Des-Arg9-bradykinin and susceptibility to inflammation

Aiguo Ni, Hang Yin, Jun Agata, Zhirong Yang, Lee Chao, Julie Chao

Research output: Contribution to journalArticle

57 Scopus citations

Abstract

We demonstrated that rat kinin B1 receptors displayed a ligand-independent constitutive activity, assessed through inositol phosphate production in transiently or stably transfected human embryonic kidney 293A cells. Substitution of Ala for Asn130 in the third transmembrane domain resulted in additional constitutive activation of the B1 receptor. The constitutively active mutant N130A receptor could be further activated by the B1 receptor agonist des-Arg9-bradykinin. To gain insights into the physiological function of the B1 receptor, we have generated transgenic mice overexpressing wild-type and constitutively active mutant receptors under the control of human cytomegalovirus immediately early gene enhancer/promoter. The rat B1 receptor transgene expression was detected in the aorta, brain, heart, lung, liver, kidney, uterus, and prostate of transgenic mice by reverse transcriptionpolymerase chain reaction/Southern blot analysis. Transgenic mice were fertile and normotensive. Overexpression of B1 receptors exacerbated paw edema induced by carrageenan and rendered transgenic mice more susceptible to lipopolysaccharide-induced endotoxic shock. Interestingly, the hemodynamic response to kinins was altered in transgenic mice, with des-Arg9-bradykinin inducing blood pressure increase when intravenously administered. Our study supports an important role for B1 receptors in modulating inflammatory responses and for the first time demonstrates that B1 receptors mediate a hypertensive response to des-Arg9-bradykinin.

Original languageEnglish
Pages (from-to)219-225
Number of pages7
JournalJournal of Biological Chemistry
Volume278
Issue number1
DOIs
StatePublished - 3 Jan 2003

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