Bradykinin and Bradykinin Antagonists Effects on Endothelial Cell Phosphoinositide Metabolism: Implications for Septic Shock
Abstract
The potent vasodilator bradykinin (BK) may be a factor in septic shock and it is known to act on the endothelium, although measurement of blood levels may present difficulties. In other tissues, there appears to be two classes of kinin receptors. BK type B1 receptors have high affinity for the agonist desarg9-BK and for the antagonist des-arg 9,(leu 8)-BK. BK type B2 receptors have high affinity for the agonists BK and Lys-BK (kallidin) and for antagonist such as (D-arg1,Hyp4,Thi6,9,D-Phe 8)- kallidin. In this report, we describe the presence of two subtypes of BK receptors on the same endothelial cell line. Measurements of inositol phosphate were used to reflect the phosphoinositide metabolism. BK elicited a 27% stimulation in phosphoinositide metabolism at 10 to the -8 power M and a 300% stimulation at 10 to the -6 power M BK. Des-arg8(leu 8)-BK (RPPGFSPF) did not block the stimulation by 10 to the - 8 power M BK, suggesting that this stimulation is not of the B1 type. BK potentiator B (pEGLPPRPKIPP) (an inhibitor of kininase II), and eledoisin (PEPSKDAFIGM) (structurally unrelated) had no effect on the basal activities or on the stimulation by 10 to the -8 power M or 10 to the -6 power M BK. These results indicate that there is some degree of specificity in the stimulation by BK, as eledoisin had no effect, and that there is no evidence for degradation of BK by kininase II. Only des-arge8,(leu 8)-BK blocked the stimulation by 10 to the -6 powder M BK. Reprints.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 1989
- Accession Number
- ADA205379
Entities
People
- David K. Wood
- Thor B. Nielson
Organizations
- Naval Medical Research Center