Multiple mechanisms in the motor responses of the guinea‐pig isolated urinary bladder to bradykinin

Abstract

1 Bradykinin (1 nM-1 μm) produced a contraction of bladder strips excised from the dome of the guinea-pig urinary bladder, an effect which was greatly enhanced by removal of the mucosal layer or by thiorphan (10 μm). All subsequent experiments were performed in mucosa-free strips and in the presence of thiorphan. 2 In carbachol (5 μm)-contracted strips, bradykinin produced a concentration (1 nM-1 μm)-dependent transient relaxation. 3 Kallidin was slightly more potent than bradykinin in producing a contraction and a relaxation of the carbachol-induced tone. By contrast, [des-Arg⁹]-bradykinin, a selective B₁ receptor agonist was barely effective up to 1 μm. 4 The contractile response to bradykinin was: (a) unaffected by either tetrodotoxin (1 μm), in vitro capsaicin desensitization (10 μm for 30 min) or apamin (0.1 μm); (b) antagonized by indomethacin (5 μm), the prostaglandin receptor antagonist SC-19220 (100 μm) or the B₂ receptor antagonist [D-Arg⁰, Hyp³, Thi^5,8, Phe⁷]-bradykinin (10 μm) and (c) almost abolished by nifedipine (1 μm). 5 The antagonism of the contractile response to bradykinin produced by indomethacin and SC-19220 was non-additive while that produced by indomethacin and the B₂ receptor antagonist was additive. 6 The relaxant response to bradykinin was unaffected by tetrodotoxin, in vitro capsaicin desensitization or indomethacin but antagonized in a competitive manner by the B₂ receptor antagonist. Further, this response was abolished by apamin (0.1 μm) but unaffected by glibenclamide (1 μm). 7 Bradykinin (10 μm) produced a consistent release of calcitonin gene-related peptide-like immunoreactivity (CGRP-LI) but not substance P-LI from the guinea-pig bladder muscle. CGRP-LI release by bradykinin was greatly reduced in bladders exposed to indomethacin. [des-Arg⁹]-bradykinin (10 μm) was ineffective. 8 We conclude that: (a) bradykinin-induced contraction involves activation of both B₂ receptors and prostanoid synthesis, via distinct mechanisms which act by inducing calcium influx via nifedipine-sensitive channels; (b) bradykinin-induced relaxation involves activation of B₂ receptors and opening of apamin-sensitive potassium channels; (c) bradykinin stimulates sensory nerves in this tissue largely via prostanoid production.