1 The aim of this study was to analyse the pharmacological characteristics, and second-messenger coupling-mechanisms, of bradykinin B1 receptors in an intact tissue, the rabbit urinary bladder; and to investigate the influence of inhibition of endogenous peptidases on kinin activities. 2 In preparations of rabbit mucosa-free urinary bladder, at 90 min after mounting of the preparations, bradykinin (1 nM-10 fM) evoked contractile responses. In contrast, the B1 receptor-selective agonist [des-Argl-BK (10 nM-10-JM) was only weakly active at this time. Contractile responses to [des-Argl-BK increased with time of tissue incubation in the organ bath, reaching a maximum after 3 h, when the pD2 estimates were 6.4 ± 0.3 for bradykinin, and 6.9 + 0.2 for [des-Arg9]-BK. [Leu8,des-Argj-BK inhibited responses to bradykinin under these conditions (n = 4). and B2 receptors, but does not require conversion by peptidases in order to activate B1 receptors. We demonstrate, for the first time, B. receptor-coupling to phosphatidylinositol hydrolysis in an intact tissue preparation.

1 In the smooth muscle of the guinea-pig taenia caeci, bradykinin produces a relaxation followed by a contraction. In the presence of hexamethonium and guanethidine, both these phases of the response were insensitive to tetrodotoxin (100 nM), w-conotoxin GVIA (100 nM) and ibuprofen (1 PiM) 6 These data suggest that in the guinea-pig taenia caeci, the five aspects of the action of bradykinin studied (the relaxant and the contractile elements of the biphasic mechanical response, the contractile response in a depolarizing high-K' solution medium and zero-Ca2+ media, and stimulation of phosphatidylinositol turnover), all result from activation of B2 receptors. A possible causal relationship is suggested between these B2 receptor-mediated membrane potential-dependent, and -independent events, and their roles in excitation contraction coupling.

1 This study investigated the effect of the recently described non-peptide bradykinin B2 receptor antagonist, WIN 64338 ([[4-[[2-[[bis(cyclohexylamino) Barabe, 1980;Hall, 1992) and, in general, the acute proinflammatory effects Author for correspondence. of kinins are mediated via stimulation of the B2 receptor type (Hall, 1992;Geppetti, 1993). Recently, Salvino and colleagues (Salvino et al., 1993;Sawutz et al., 1994) announced the development of the first relatively high affinity non-peptide bradykinin B2 receptor antagonist, WIN 64338, MethodsRabbit iris sphincter Male New Zealand albino rabbits (2.5-3.0 kg) were killed by an i.v. overdose of pentobarbitone sodium. The eyes were enucleated immediately after death and opened by a midline incision 2 -3 mm dorsal to the limbus, followed by excision of Bdft Joumal of Phanucology (IM) 116, 3164 -3-168

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