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

Abstract

1 Bradykinin (1 nM-i gM) 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 (10pM). All subsequent experiments were performed in mucosa-free strips and in the presence of thiorphan. 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 M) but unaffected by glibenclamide (1 pM).7 Bradykinin (10pM) 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 (10pM) 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.

The Use of the Isolated Mouse Whole Bladder for Investigating Bladder Overactivity

“…It also enhanced the response to neuronally mediated bladder contractions. These findings agree with previous evidence that bradykinin acts by sensitizing the primary afferent nerves either through release of sensory neuropeptides from nerve terminals (Marceau et al, 1980;Maggi et al, 1989) or by direct stimulation of bladder afferent nerves (Lecci et al, 1995). It is therefore reasonable to suggest that bradykinin potentiation of neuronally mediated bladder contraction seen in this model is due to the sensitization of intramural nerves and could thus mimic the pathophysiological process involved in chronic inflammation.…”

“…One of the contributing factors to these conditions is a functional change in the primary afferents brought about by the sensitization of both mechanosensitive and C-fibers afferents by potent inflammatory mediators such as bradykinin (Marceau et al, 1980;Maggi et al, 1989). Evidence has linked the activity of bradykinin to efferent purinergic neurotransmission in rat isolated muscle strips (Acevedo et al, 1990;Patra and Westfall, 1996).…”

Pharmacology of the Lower Urinary Tract: Basis for Current and Future Treatments of Urinary Incontinence

“…The contractile effects of the ETs in the detrusor seem to involve both activation of L-type Ca 2ϩ channels and activation of phospholipase C (Maggi et al, 1989e;Garcia-Pascual et al, 1990Persson et al, 1992a). Thus, in the pig detrusor, contractile effects were associated with an increase in IP 3 concentrations and were blocked by the protein kinase C inhibitor, H-7, and by nifedipine (Persson et al, 1992a).…”

“…The contractile effect was significantly increased after pretreatment with captopril or enalaprilate, which suggests that ACE inhibitors may reduce the degradation of bradykinin in the human detrusor. Maggi et al (1989e) found that multiple mechanisms were involved in the motor responses of the guinea pig isolated bladder to bradykinin. They found that bradykinin-induced contraction involved activation of both B2 receptors and prostanoid synthesis.…”

Characterization of the capsaicin‐sensitive component of cyclophosphamide‐induced inflammation in the rat urinary bladder

“…activity of these neurones is achieved by the release of several neuropeptides (Maggi et al, 1987;1988a,b) many of which possess inflammatory activity, producing what is termed neurogenic inflammation (for reviews see Chahl, 1988;Maggi, 1991). In turn, various mediators of inflammation, such as bradykinin (Maggi et al, 1989;1993) and formylmethionyl-leucyl phenylalanine have been shown to induce release of neuropeptides from sensory nerve endings in the urinary bladder. Further evidence for the inflammatory activity of sensory neuropeptides has been demonstrated by the fact that the acute administration of capsaicin itself will result in a plasma protein extravasation (PPE) (Maggi et al, 1987) and that a variety of stimuli for sensory nerves in the bladder, such as xylene and hypertonic solutions, produce inflammatory effects that are dependent upon the existence of an intact sensory afferent system, the response being modified by capsaicin treatment (Maggi et al, 1988b).…”