Pharmacological analysis of the local and reflex responses to bradykinin on rat urinary bladder motility in vivo.
1. The topical application of bradykinin (BK) (0.05-5000 pmol/rat) onto the serosal surface of the urinary bladder in urethane-anaesthetized rats, evoked low amplitude tonic contractions (not exceeding 25 mmHg) or high amplitude (about 50 mmHg), phasic reflex contractions (chemoceptive micturition reflex) which were abolished by bilateral ablation of the pelvic ganglia. In ganglionectomized rats, BK induced only a local, tonic-type contraction. 2. Systemic capsaicin pretreatment (164 mumol kg-1, 4 days before) reduced the incidence of chemoceptive reflex induced by BK (500 pmol/rat) but had no effect on the magnitude of the tonic-type contraction elicited by BK in ganglionectomized rats. Indomethacin (11 mumol kg-1, 20 min before) reduced the incidence but not the amplitude of the reflex contractions induced by topical application of BK (500 pmol/rat). In ganglionectomized rats, indomethacin (11 mumol kg-1, 20 min before) decreased the amplitude of the tonic contraction evoked by BK. Indomethacin did not affect the chemoceptive reflex induced by topical application of capsaicin (15 nmol/rat) onto the bladder. 3. Intrathecal administration of the tachykinin NK1 receptor antagonists, RP 67,580 (10 nmol/rat) or SR 140,333 (10 nmol/rat), abolished the chemoceptive reflex induced by BK without modifying the magnitude of the tonic contraction. SR 140,333 (10 nmol/rat) also abolished the occurrence of the chemoceptive reflex induced by capsaicin. 4. Intravenous administration of the B2 receptor antagonist, Hoe 140 (35 nmol kg-1, 10 min before) abolished the reflex and local effects induced by BK on bladder motility but failed to modify the chemoceptive reflex induced by topical application of capsaicin (15 nmol/rat). 5. Intrathecal administration of Hoe 140 (10 nmol/rat) reduced the incidence of the chemoceptive reflex induced by BK but had no effect on the amplitude of the local motor response. Likewise, Hoe 140(10 nmol/rat, i.t.) reduced the incidence of reflex bladder contractions induced by topical application of capsaicin (15 nmol/rat) without affecting the magnitude of the tonic-type contraction.6. These findings indicate that BK stimulates motility through B2 receptors in the rat urinary bladder.BK activates the reflex response by stimulating capsaicin-sensitive afferent nerves with a contribution from prostanoids. At the spinal cord level, tachykinin NK1 and BK B2 receptors could also be involved in the chemoceptive reflex induced by BK or capsaicin.
Lecci
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A
Pharmacology Research Dept., A. Menarini Pharmaceuticals, Florence, Italy.
Giuliani
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S
Meini
S
S
Maggi
C A
CA
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001920:Bradykinin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology*; D002211:Capsaicin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007211:Indoles / Q000008:administration & dosage / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007278:Injections, Spinal; D054833:Isoindoles; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology; D011812:Quinuclidines / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012018:Reflex / Q000187:drug effects; D013373:Substance P / Q000037:antagonists & inhibitors; D001743:Urinary Bladder / Q000187:drug effects* / Q000378:metabolism
D000319:Adrenergic beta-Antagonists; D007211:Indoles; D054833:Isoindoles; D010880:Piperidines; D011812:Quinuclidines; C071693:7,7-diphenyl-2-(1-imino-2-(2-methoxyphenyl)ethyl)perhydroisoindol-4-one; C085215:SR 140333; D013373:Substance P; C065679:icatibant; D002211:Capsaicin; D001920:Bradykinin; D007213:Indomethacin