A useful and sensitive method for demonstration of the involvement of either kallikrein-kinin system in pathological states.
In rat carrageenin-induced pleurisy, bradykinin (BK) was hardly able to be detected (< 160 pg per rat) in the exudates. In contrast, des-Phe8-Arg9-BK (des-8,9-BK) level, determined by an enzyme immunoassay (EIA) newly developed, was larger in the exudate and the levels were kept throughout the entire course of this inflammation. Arg-Pro-Pro-Gly-Phe ([1-5] BK) level, measured by an EIA newly developed, was much higher than that of des-8,9-BK in the exudate. Intrapleural administration of soy bean trypsin inhibitor (0.3 mg per rat) reduced the levels of both des-8,9-BK and [1-5] BK in the exudates. Reduction in the residual levels of plasma prekallikrein (P-Kall) and high-molecular-weight-kininogen (HMW-K), not low-molecular-weight-kininogen (LMW-K), were accompanied with increase in these BK degradation products, indicating that plasma prekallikrein was activated in the pleural cavity. On the other hand, intravenous injection of acetaldehyde to rats pretreated with disulfiram resulted in the significant increase in the levels of [1-5] BK in the blood, which was accompanied with reduction in the residual levels of LMW-K, not of HMW-K and P-Kall in plasma. These results indicated that the detection of BK degradation products was a good marker for the kinin release in vivo and that the concomitant reduction of the precursor proteins allowed us to identify the type of kallikrein-kinin systems relevant to the kinin release.
Majima
M
M
Department of Pharmacology, Kitasato University School of Medicine, Kanagawa, Japan.
Sunahara
N
N
Uchida
Y
Y
Katori
M
M
D000079:Acetaldehyde / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D001920:Bradykinin / Q000737:chemistry / Q000378:metabolism; D002351:Carrageenan; D004221:Disulfiram / Q000494:pharmacology; D007124:Immunoenzyme Techniques; D016234:Kallikrein-Kinin System / Q000187:drug effects / Q000502:physiology*; D007705:Kinins / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D010998:Pleurisy / Q000209:etiology / Q000378:metabolism; D011498:Protein Precursors / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D007705:Kinins; D011498:Protein Precursors; D002351:Carrageenan; D000079:Acetaldehyde; D001920:Bradykinin; D004221:Disulfiram