Activation of alpha1D adrenergic receptors in the rat urothelium facilitates the micturition reflex.
OBJECTIVE
Previous studies have revealed that the activation of alpha(1) adrenergic receptors in urothelial cells releases neurotransmitters. We determined if alpha(1D) adrenergic receptors are expressed in the urothelium of the rat bladder and if inhibition of these receptors affects reflex voiding.


METHODS
Female Wistar rats were used in the experiments. Receptor expression was evaluated by Western blot. The effects of receptor activation were studied using cystometrograms, measurement of adenosine triphosphate concentrations in the bladder lumen and afferent nerve recording. The alpha(1D) antagonist naftopidil (0.75 to 1.66 mg/kg) was administered intravenously into the external jugular vein.


RESULTS
The expression of alpha(1D) adrenergic receptors was detected in urothelial tissue with Western blot and immunohistochemistry. The alpha(1D) receptor antagonist naftopidil prolonged the intercontraction interval during continuous infusion cystometrograms in conscious rats (143% of the control value) and suppressed the excitatory effect of intravesical infusion of acetic acid (0.1%) on the intercontraction interval (220%). Naftopidil inhibited the bladder afferent nerve activity induced by bladder distention (32.0%) and acetic acid infusion (30.4%), and decreased adenosine triphosphate levels in the bladder perfusate during bladder distention (36.6%).


CONCLUSIONS
Endogenous catecholamines appear to act on alpha(1D) receptors in the urothelium to facilitate mechanosensitive bladder afferent nerve activity and reflex voiding.
Ishihama
Hiroko
H
Department of Neurophysiology, Akita University, School of Medicine, Akita, Japan.
Momota
Yoshiharu
Y
Yanase
Haruko
H
Wang
Xiaojun
X
de Groat
William C
WC
Kawatani
Masahito
M
D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D008297:Male; D009281:Naphthalenes / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology*; D012018:Reflex / Q000187:drug effects / Q000502:physiology*; D014554:Urination / Q000187:drug effects / Q000502:physiology*; D019459:Urothelium / Q000187:drug effects / Q000502:physiology*
C547721:Adra1d protein, rat; D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D009281:Naphthalenes; D010879:Piperazines; D018340:Receptors, Adrenergic, alpha-1; C064357:naftopidil