Pharmacological characterization of RMP-7, a novel bradykinin agonist in smooth muscle

• Published in: Immunopharmacology 1999-12, Vol.45 (1-3), p.63-67
• Main Authors: Shimuta, Suma I, Barbosa, Ana M.R.B, Borges, Antonio C.R, Paiva, Therezinha B
• Format: Article
• Language: English
• Subjects: Angiotensin-converting enzyme; Animals; B2 receptors; Biological and medical sciences; Bradykinin; Bradykinin - agonists; Bradykinin - analogs & derivatives; Bradykinin - antagonists & inhibitors; Bradykinin - pharmacology; Guinea Pigs; Guinea-pig ileum; Ileum - chemistry; Ileum - drug effects; Medical sciences; Mesenteric Arteries - chemistry; Mesenteric Arteries - drug effects; Mesenteric artery; Muscle Contraction - drug effects; Muscle, Smooth - chemistry; Muscle, Smooth - drug effects; Muscle, Smooth, Vascular - chemistry; Muscle, Smooth, Vascular - drug effects; Neuropharmacology; Neurotransmitters. Neurotransmission. Receptors; Peptidergic system (neuropeptide, opioid peptide, opiates...). Adenosinergic and purinergic systems; Pharmacology. Drug treatments; Rats; RMP-7
• ISSN: 0162-3109
• DOI: 10.1016/S0162-3109(99)00150-2

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 μM) 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 μM 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.