Role of supraspinal serotonin receptors for micturition in normal conscious rats.
Serotonin (5-HT) receptors are widely distributed in the central nervous system, including several areas involved in the control of micturition reflex pathways. However, the roles of the different subtypes of 5-HT receptors are not well known. We studied in normal, conscious rats, the effects on the cystometrogram of intracerebroventricular (i.c.v.) administration of 5-HT, 8-hydroxy-2-(di-N-propylaminotetralin) (8-OH-DPAT; agonist at 5-HT(1A) receptors), alpha-methyl-5-hydroxytryptamine maleate (agonist at 5-HT(2) receptors), 2-methyl-5-hydroxytryptamine hydrochloride (agonist at 5-HT(3) receptors), and 1-(4-amino-5-chloro-2methoxyphenyl)-3-(1-n-butyl-4piperidinyl)-1-propanone hydrochloride (RS67506; agonist at 5-HT(4) receptors). Female Sprague-Dawley rats, weighing approximately 230 g, were used. A polyethylene catheter was inserted into the bladder through the dome for cystometric investigations. For administration of drugs, a catheter was implanted into the right cerebral ventricle. Three days after implantation of the bladder catheter, continuous cystometry was performed. Administration of 5-HT (6 nmol/kg i.c.v.), 8-OH-DPAT (6 nmol/kg), alpha-methyl-5-hydroxytryptamine maleate (6 nmol/kg), or RS67506 hydrochloride (6 nmol/kg) significantly (P < 0.05) increased micturition pressure and decreased bladder capacity and micturition volume. The effects increased in a dose-dependent manner (18, 60 nmol/kg). Intracerebroventricular administration of 2-methyl-5-hydroxytryptamine hydrochloride (60 nmol/kg) caused no change in the cystometric parameters. The results suggest that in normal conscious rats, at the supraspinal level, 5-HT (via 5-HT(1A), 5-HT(2), and 5-HT(4) receptors) can enhance the micturition reflex induced by bladder filling. Whether this means that 5-HT(1A), 5-HT(2), and 5-HT(4) receptors can be targets for drugs meant for treatment of bladder hyperactivity, should be explored.
Ishizuka
Osamu
O
Department of Urology, Shinshu University School of Medicine, Matsumoto, Japan. ishizuk@hsp.md.shinshu-u.ac.jp
Gu
Baojun
B
Igawa
Yasuhiko
Y
Nishizawa
Osamu
O
Pehrson
Rikard
R
Andersson
Karl-Erik
KE
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000502:physiology*; D005260:Female; D007276:Injections, Intraventricular; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000502:physiology; D012701:Serotonin / Q000031:analogs & derivatives* / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology* / Q000627:therapeutic use; D013449:Sulfonamides / Q000494:pharmacology; D001743:Urinary Bladder / Q000187:drug effects* / Q000502:physiology / Q000503:physiopathology; D014546:Urinary Catheterization; D014549:Urinary Incontinence / Q000503:physiopathology; D014554:Urination / Q000187:drug effects* / Q000502:physiology
D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; D013449:Sulfonamides; C107556:RS 67506; C042390:alpha-methylserotonin; D012701:Serotonin; C045918:2-methyl-5-HT; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin