Expression of kininogen, kallikrein and kinin receptor genes by rat cardiomyocytes.
To ascertain the existence of the kallikrein-kinin system in the heart, we have studied in vivo and in vitro whether rat cardiac tissue expresses kininogen, kallikrein and kinin receptor mRNAs. The reverse transcription-polymerase chain reaction demonstrated that the ventricular myocardium of adult male rats expressed mRNAs for T- and low-molecular-weight (L-) kininogens, tissue kallikreins such as true kallikrein and T-kininogenase, and bradykinin B2 receptor, but not those for high-molecular-weight kininogen and B1 receptor. Lipopolysaccharide (LPS; 0.5 mg/kg, i.v.) increased the levels of mRNA for T-kininogen at 12 h and the bradykinin B1 receptor at 24 h without affecting that for other components. All of these mRNAs for the kallikrein-kinin system were also detected in cultured cardiomyocytes derived from neonatal rat ventricles; dibutyryl cyclic AMP, LPS or inflammatory cytokines such as interleukin-1 and tumor necrosis factor, up-regulated mRNA expression of T-kininogen, T-kininogenase, or B1 receptor in these cells in vitro. These results suggest that there are two kinin-generating systems in rat myocardium comprising T-kininogen/T-kininogenase and L-kininogen/true kallikrein respectively, and that the former may be relatively important in inflammatory diseases or conditions in which cAMP levels increase in cardiomyocytes.
Yayama
K
K
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kobe Gakuin University, Ikawadani-cho, Nishi-ku, Kobe, Japan. yayama@pharm.kobegakuin.ac.jp
Nagaoka
M
M
Takano
M
M
Okamoto
H
H
D000818:Animals; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000494:pharmacology; D016207:Cytokines / Q000494:pharmacology; D018076:DNA, Complementary / Q000378:metabolism; D015870:Gene Expression; D006352:Heart Ventricles; D007610:Kallikreins / Q000235:genetics*; D007704:Kininogens / Q000235:genetics*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D018002:Receptors, Bradykinin / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D016207:Cytokines; D018076:DNA, Complementary; D007704:Kininogens; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D018002:Receptors, Bradykinin; D000242:Cyclic AMP; D007610:Kallikreins