Role of supraspinal tachykinins for volume- and L-dopa-induced bladder activity in normal conscious rats.
To clarify the roles of tachykinins in volume-induced micturition and in bladder hyperactivity, presumed to originate from supraspinal structures, normal, female Sprague-Dawley rats were investigated cystometrically before and after intracerebroventricular (i.c.v) administration of RP 67,580, a selective antagonist of NK-1 receptors, and/or SR 48,968, a selective antagonist of NK-2 receptors. The effects of RP 67,580 and SR 48,968 on intra-peritoneal (i.p.) L-dopa-induced bladder hyperactivity were also investigated. I.c.v. administration of RP 67,580 (20 nmol) SR 48,968 (20 nmol) suppressed micturition. Combination of i.c.v. RP 67, 580 (2 nmol) and SR 48,968 (2 nmol) significantly decreased micturition pressure (18%), and increased bladder capacity (26%), micturition volume (18%), and residual volume (223%). In rats pretreated with i.p. carbidopa 50 mg/kg, i.p. L-dopa 50 mg/kg caused bladder hyperactivity that was attenuated by the combination of i.c. v. RP 67,580 (2 nmol) and SR 48,968 (2 nmol). The results suggest that tachykinins, via stimulation of NK receptors in supraspinal structures, are involved in both volume and L-dopa-induced stimulation of bladder activity. This may imply that tachykinins can influence both the supraspinal and spinal control of the urinary bladder. It also implies that supraspinal NK receptors are a possible target for drugs aimed for elimination of bladder hyperactivity mediated via these pathways. Neurourol. Urodynam. 19:101-109, 2000.
Ishizuka
O
O
Department of Urology, Shinshu University School of Medicine, Matsumoto, Japan. ishizuk@hsp.md.shinshu-u.ac.jp
Igawa
Y
Y
Nishizawa
O
O
Andersson
K E
KE
D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D001921:Brain / Q000378:metabolism*; D005260:Female; D007211:Indoles / Q000494:pharmacology; D007276:Injections, Intraventricular; D054833:Isoindoles; D007980:Levodopa / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008751:Methylene Blue / Q000008:administration & dosage / Q000493:pharmacokinetics; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018041:Receptors, Neurokinin-2 / Q000037:antagonists & inhibitors; D012016:Reference Values; D015320:Tachykinins / Q000502:physiology*; D014018:Tissue Distribution; D001743:Urinary Bladder / Q000187:drug effects* / Q000502:physiology*; D014556:Urine / Q000502:physiology*
D001549:Benzamides; D007211:Indoles; D054833:Isoindoles; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines; D018041:Receptors, Neurokinin-2; D015320:Tachykinins; C071693:7,7-diphenyl-2-(1-imino-2-(2-methoxyphenyl)ethyl)perhydroisoindol-4-one; D007980:Levodopa; C073839:SR 48968; D008751:Methylene Blue