Biological actions of a novel non-
peptide B2 receptor agonist,
FR190997, were examined by comparing them with those of
bradykinin. The paw
edema was induced by
subcutaneous injection of 30 microl of
solution of
bradykinin (0.3, 0.6, and 1.2 nmol) or
FR190997 (0.1, 0.3, and 0.9 nmol) into the right hind paw of ICR male mice.
Bradykinin caused a dose-dependent
edema formation, which peaked at 15 min and ceased after 150 min.
FR190997 also formed a dose-dependent
edema, peaking at 15-30 min with a slight delay compared to
bradykinin and this response continued over 200 min. The
edema formed by
bradykinin or
FR190997 was inhibited by pretreatment with
HOE140 (1 mg/kg) injected intraperitoneally 30 min before the injection of each agonist. A novel non-
peptide B2 antagonist,
FR173657 (30 mg/kg, i.p. 30 min before the agonist), also diminished these responses by
bradykinin and
FR190997 dose-dependently.
Indomethacin (10 mg/kg, i.p. 30 min before) inhibited the response to
FR190997, suggesting that release of
prostaglandins induced by the B2 agonistic action might be involved in this inflammatory process induced by
FR190997. The hypotensive action of
FR190997 was also examined. Intravenously injected
FR190997 caused the systemic hypotensive response in Sprague-Dawley male rats anesthetized with
pentobarbital. The potency of
FR190997 was weaker than that of
bradykinin, when compared with the maximal
hypotension. Duration of the hypotensive response of
FR190997 was significantly longer than that of
bradykinin. These results indicate that
FR190997 has the B2 agonistic action similar to
bradykinin and is also a good tool for in vivo examination of the B2 receptor.