The relationship between α1-adrenergic receptors and TRPM8 channels in detrusor overactivity induced by cold stress in ovariectomized rats.
OBJECTIVE
We studied whether cold stress induced detrusor overactivity in ovariectomized rats is associated with increased thermosensitive TRPM8 channel expression in the skin and whether the response could be inhibited by α1-adrenergic receptor blockade.


METHODS
A total of 24 Sprague-Dawley® rats at postnatal week 30 were randomly selected for ovariectomy (16) or sham ovariectomy (8). Five weeks later cystometric measurements of conscious, freely moving rats were made at room temperature (mean ± SEM 28C ± 2C) for 20 minutes. Eight ovariectomized rats were intravenously administered 1.0 mg/kg naftopidil. The other 8 ovariectomized and 8 sham operated rats were given naftopidil-free vehicle. Five minutes later they were transferred to a low temperature environment (mean 4C ± 2C) and micturition patterns were again recorded. TRPM8 channel expression in lumbar skin was estimated by real-time reverse-transcriptase polymerase chain reaction and immunohistochemistry.


RESULTS
TRPM8 channel mRNA and protein in the skin of ovariectomized rats were significantly higher than in sham operated rats. At room temperature micturition parameters were similar in sham operated and ovariectomized rats. At low temperature sham operated and ovariectomized rats showed cold stress induced detrusor overactivity but increased micturition frequency and decreased bladder capacity were significantly greater in ovariectomized rats. Treatment of ovariectomized rats with naftopidil inhibited cold stress induced detrusor overactivity.


CONCLUSIONS
Cold stress induced detrusor overactivity in rats with decreased estrogen is associated with TRPM8 channel up-regulation in the skin and mediated by nerve pathways using α1-adrenergic receptors.
Department of Urology, Shinshu University School of Medicine, Matsumoto, Japan.
Wataru
W
Noguchi
Osamu
O
Ishizuka
Tetsuya
T
Imamura
Yoshiki
Y
Kurizaki
Takahiro
T
Yamagishi
Hitoshi
H
Yokoyama
Zhang
Z
Lei
Sudha Gautam
SG
Silwal
Osamu
O
Nishizawa
Karl-Erik
KE
Andersson
D000818:Animals; D003080:Cold Temperature; D005260:Female; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology*; D013312:Stress, Physiological; D050053:TRPM Cation Channels / Q000502:physiology*; D053201:Urinary Bladder, Overactive / Q000209:etiology*
D018340:Receptors, Adrenergic, alpha-1; D050053:TRPM Cation Channels; C498947:Trpm8 protein, rat