WIN 64338 hydrochloride is a potent and competitive antagonist of bradykinin B2 receptor [1].
Bradykinin B2 receptor is a G-protein coupled receptor for bradykinin. Bradykinin is an inflammatory nonapeptide and plays a critical role in edema, vasodilation, pain fiber stimulation and smooth muscle spasm.
WIN 64338 hydrochloride is a potent and competitive bradykinin B2 receptor antagonist. In human IMR-90 cells, WIN 64338 inhibited bradykinin binding to the bradykinin B2 receptor with Ki value of 64 nM and inhibited Ca2+ efflux stimulated by bradykinin with pA2 value of 7.1 in a competitive way. WIN 64338 inhibited guinea pig ileum contractility induced by bradykinin with pA2 value of 8.2 and also inhibited acetyicholine-induced contractility [1]. In iris sphincter isolated from rabbit, WIN 64338 (1-10 μM) inhibited contractile responses evoked by bradykinin with pKB value of 6.6 [2]. In guinea-pig tracheal smooth muscle cells, WIN 64338 inhibited inositol phosphate formation induced by bradykinin [3].
In guinea-pigs, WIN 64338 (30 nM) significantly inhibited the increases in plasma extravasation induced by bradykinin via the release of tachykinins from the trigeminal nerve [2].
References:
[1]. Sawutz DG, Salvino JM, Dolle RE, et al. The nonpeptide WIN 64338 is a bradykinin B2 receptor antagonist. Proc Natl Acad Sci U S A, 1994, 91(11): 4693-4697.
[2]. Hall JM, Figini M, Butt SK, et al. Inhibition of bradykinin-evoked trigeminal nerve stimulation by the non-peptide bradykinin B2 receptor antagonist WIN 64338 in vivo and in vitro. Br J Pharmacol, 1995, 116(8): 3164-3168.
[3]. Scherrer D, Schmidlin F, Lach E, et al. Effect of WIN 64338, a B2 bradykinin receptor antagonist on guinea-pig tracheal smooth muscle cells in culture. Fundam Clin Pharmacol, 1998, 12(2): 188-193.