Pharmacological characterization of RMP-7, a novel bradykinin agonist in smooth muscle.
RMP-7 is a bradykinin (BK) agonist designed to be resistant to kininases such as angiotensin-converting enzyme (ACE). Pharmacological assays were performed with RMP-7 in isolated guinea-pig ileum and rat mesenteric artery. RMP-7 induced contractile responses in the guinea-pig ileum, where the apparent affinity of the peptide (pD2) was significantly lower than that determined for BK (7.3 +/- 0.07 vs. 8.3 +/- 0.05, respectively). HOE-140 blocked this effect indicating that B2 receptor was involved. Captopril (1 microM) had no potentiating effect on RMP-7 but increased pD2 value determined for BK (8.8 +/- 0.1), confirming a high resistance of RMP-7 to the ACE. In rat mesenteric artery, RMP-7 induced endothelium-dependent relaxation (7.8 +/- 0.4), with a higher affinity than that of BK which induced vasodilatation only in the presence of 1 microM captopril (6.9 +/- 0.36). Nevertheless, the maximum effect induced by RMP-7 was lower than that of BK in contrast to that observed in guinea-pig ileum although B2 receptor was involved in both cases. We concluded that: RMP-7 is greatly resistant to the ACE and that the receptor sites activated by RMP-7 and BK show important differences in vascular and non-vascular preparations probably due to the different sensitivity of the B2 receptor to RMP-7.
Shimuta
S I
SI
Department of Biophysics, Escola Paulista de Medicina, São Paulo, SP Brazil.
Barbosa
A M
AM
Borges
A C
AC
Paiva
T B
TB
D000818:Animals; D001920:Bradykinin / Q000819:agonists* / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D006168:Guinea Pigs; D007082:Ileum / Q000737:chemistry / Q000187:drug effects; D008638:Mesenteric Arteries / Q000737:chemistry / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000737:chemistry / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000737:chemistry* / Q000187:drug effects*; D051381:Rats
C089876:RMP 7; C065679:icatibant; D001920:Bradykinin