Inhibition of urinary bladder motility by a spinal action of U-50488H in rats

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  • Akinobu Gotoh
    Division of Urology, Department of Organs Therapeutics, Faculty of Medicine, Kobe University Graduate School of Medicine, 7–5–2 Kusunoki-cho, Chuo-ku, Kobe, Hyogo 650–0017, Japan
  • Kazuhiro Goto
    Kampo & Pharmacognosy Laboratories, Tsumura & Co., 3586 Yoshiwara, Ami-machi, Ibaraki 300–1192, Japan
  • Atsushi Sengoku
    Division of Urology, Department of Organs Therapeutics, Faculty of Medicine, Kobe University Graduate School of Medicine, 7–5–2 Kusunoki-cho, Chuo-ku, Kobe, Hyogo 650–0017, Japan
  • Toshiro Shirakawa
    Division of Urology, Department of Organs Therapeutics, Faculty of Medicine, Kobe University Graduate School of Medicine, 7–5–2 Kusunoki-cho, Chuo-ku, Kobe, Hyogo 650–0017, Japan
  • Yoshinobu Akao
    Division of Urology, Department of Organs Therapeutics, Faculty of Medicine, Kobe University Graduate School of Medicine, 7–5–2 Kusunoki-cho, Chuo-ku, Kobe, Hyogo 650–0017, Japan
  • Masato Fujisawa
    Division of Urology, Department of Organs Therapeutics, Faculty of Medicine, Kobe University Graduate School of Medicine, 7–5–2 Kusunoki-cho, Chuo-ku, Kobe, Hyogo 650–0017, Japan
  • Hiroshi Okada
    Division of Urology, Department of Organs Therapeutics, Faculty of Medicine, Kobe University Graduate School of Medicine, 7–5–2 Kusunoki-cho, Chuo-ku, Kobe, Hyogo 650–0017, Japan
  • Soichi Arakawa
    Division of Urology, Department of Organs Therapeutics, Faculty of Medicine, Kobe University Graduate School of Medicine, 7–5–2 Kusunoki-cho, Chuo-ku, Kobe, Hyogo 650–0017, Japan
  • Hiroshi Sasaki
    Kampo & Pharmacognosy Laboratories, Tsumura & Co., 3586 Yoshiwara, Ami-machi, Ibaraki 300–1192, Japan
  • Sadao Kamidono
    Division of Urology, Department of Organs Therapeutics, Faculty of Medicine, Kobe University Graduate School of Medicine, 7–5–2 Kusunoki-cho, Chuo-ku, Kobe, Hyogo 650–0017, Japan

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<jats:title>Abstract</jats:title><jats:p>We examined the effect of a kappa agonist, U-50488H, upon the bladder motility of anaesthetized rats. The frequency of distension-induced rhythmic bladder contractions was reduced by the intravenous (10 mg kg−1) or intrathecal (10–100 μg) administration of U-50488H. The effect of intravenous U-50488H was inhibited by pre-treatment with nor-binaltorphimine (10 mg kg−1, s.c.). The inhibition of bladder contractions by intrathecal U-50488H (30 μg) was eliminated with the concomitant use of nor-binaltorphimine (10 mg kg−1, s.c.), and diminished by reserpine (4 mg kg−1, i.p.), yohimbine (10 μg, i.t.) or methysergide (20 μg, i.t.). The amplitude of bladder contractions induced by an electrical stimulation of the pontine micturition centre was not inhibited by intrathecal U-50488H (30 and 100 μg). These results suggested that a kappa agonist could inhibit micturition reflex as well as other opioids, and at least part of the inhibition was due to the diminishment of bladder sensation based on the activation of the descending monoaminergic systems through the spinal kappa-opioid receptors.</jats:p>

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