DIFFERENT B-1 KININ RECEPTOR EXPRESSION AND PHARMACOLOGY IN ENDOTHELIAL-CELLS OF DIFFERENT ORIGINS AND SPECIES

In bovine aortic endothelial cells (BAECs), we previously demonstrated B-1 and B-2 kinin receptor-mediated increases in intracellular guanos ine-3',5'-cyclic monophosphate (cGMP). In this study, the B-2 kinin re ceptor agonist bradykinin increased cGMP in rat microvascular coronary endothelial cells (RMCECs) and human umbilical vein endothelial cells (HUVECs), which could be prevented with the specific B-2 kinin recept or antagonist icatibant but not with the B-1 kinin receptor antagonist des-Arg(9)-[Leu(8)]bradykinin or with the nonpeptide kinin receptor a ntagonist WIN 64338. B-2 kinin receptor mRNA could be detected in all three cell types using reverse transcription-polymerase chain reaction and subsequent Southern blotting. The B-1 kinin receptor agonist des- Arg(9)-bradykinin increased cGMP in RMCECs but not in HUVECs. The resp onse in RMCECs could be prevented by des-Arg(9)-[Leu(8)]bradykinin as well as by WIN 64338 but not by icatibant. in BAECs, the B-1 kinin rec eptor-mediated cGMP synthesis could be prevented by icatibant and dese nsitized by preincubation with des-Arg(9)-bradykinin as well as bradyk inin. We detected B-1 kinin receptor mRNA in RMCECs and HUVECs but not in BAECs. In HUVECs, the detection of B-1 kinin receptor mRNA is in c ontradiction to the cGMP measurements. In BAECs, the atypical B-1 kini n receptor pharmacology, the heterologous desensitization of the recep tor and the failure to detect B-1 kinin receptor mRNA cannot be explai ned by a typical B-1 kinin receptor subtype. Thus, B-2 kinin receptors with similar pharmacology are constitutively expressed in each of the three endothelial cell types. However, the endothelial cell types are heterogeneous in the expression of typical B-1 kinin receptors and th e pharmacology of the B-1 kinin receptor-mediated responses.