Bladder distension and activation of the efferent function of sensory fibres: similarities with the effect of capsaicin.
1. The effects of the tachykinin NK2 receptor antagonist MEN 11420 (100 nmol kg(-1), i.v.) and isoprenaline (400 nmol kg(-1), i.v.) were compared in a model of distension-induced bladder activity in isovolumetric conditions. MEN 11420 induced a relaxation of the basal tone of the urinary bladder that was dependent on the volume of the viscus: the effect was absent at low volumes (0.2 and 0.5 ml) and it was maximal at high volumes of distension (1 and 2 ml), approaching about 60% of the isoprenaline-induced relaxation. The relaxant effect of isoprenaline was always evident at all volumes of distension. 2. Tetrodotoxin (1-100 microM, intravesically applied) abolished distension-evoked micturition contractions, but did not prevent the relaxant effect of MEN 11420- or isoprenaline on the bladder tone. 3. The cyclo-oxygenase inhibitor S-ketoprofen (0.5 micromol kg(-1), i.v.) produced a marked decrease of the bladder tone and a concomitant reduction of bladder motility at 1 ml volume of distension. At 2 ml of distension, S-ketoprofen still decreased the minimal pressure but had no significant effect on other parameters of vesical motility. In S-ketoprofen-pretreated rats, the relaxant effect of MEN 11420 was significant at 2 but not at 1 ml of distension, and that of isoprenaline was reduced by 50% at both 1 and 2 ml. 4. Ruthenium red (10 micromol kg(-1), i.v.) had no effect at a low volume of distension (0.2 ml) or at highest volume (2 ml) but decreased the basal tone and the frequency of bladder contractions at 1 ml of distension. In ruthenium red-pretreated rats, MEN 11420 failed to decrease bladder tone at 1 ml, whereas at 2 ml the effect of MEN 11420 was not different from that observed in controls (43 vs 60% of isoprenaline-induced relaxation, respectively). 5. At both 1 and 2 ml of distension, capsaicin pretreatment (164 micromol kg(-1), s.c. 5 days before) reduced the frequency of micturition contractions but had no effect on the bladder tone. Capsaicin pretreatment prevented the relaxant effect of MEN 11420 on the bladder tone both at 1 and at 2 ml of distension. 6. It is concluded that the release of tachykinins from capsaicin-sensitive afferent nerves induced by bladder distension is resistant to tetrodotoxin and to prostaglandin synthesis inhibition. Tachykinins modulate the vesical tone by acting through NK2 receptors.
Lecci
A
A
Pharmacology Research Department Menarini Ricerche, Florence, Italy.
Giuliani
S
S
Tramontana
M
M
Santicioli
P
P
Criscuoli
M
M
Dion
S
S
Maggi
C A
CA
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D002211:Capsaicin / Q000494:pharmacology*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004347:Drug Interactions; D007545:Isoproterenol / Q000494:pharmacology; D007660:Ketoprofen / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D009412:Nerve Fibers / Q000187:drug effects* / Q000502:physiology; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology; D010456:Peptides, Cyclic / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018039:Receptors, Tachykinin / Q000037:antagonists & inhibitors; D012430:Ruthenium Red / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D001743:Urinary Bladder / Q000187:drug effects* / Q000294:innervation
D000318:Adrenergic beta-Agonists; D016861:Cyclooxygenase Inhibitors; C107754:MEN 11420; D010456:Peptides, Cyclic; D018039:Receptors, Tachykinin; D012430:Ruthenium Red; D013779:Tetrodotoxin; D007660:Ketoprofen; D007545:Isoproterenol; D002211:Capsaicin