Differential roles of peripheral and spinal endothelin receptors in the micturition reflex in rats

Teruyuki Ogawa, Izumi Kamo, Beth Pflug, Joel B. Nelson, Satoshi Seki, Yasuhiko Igawa, Osamu Nishizawa, William C. De Groat, Michael B. Chancellor, Naoki Yoshimura

Research output: Contribution to journalArticle

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Abstract

Purpose: We investigated the effects of endothelin (ET) receptor activation in the bladder and the spinal cord on the micturition reflex in urethane anesthetized rats. Materials and Methods: The effects of ET receptor activation on bladder activity were examined during continuous infusion cystometrograms. ET-1 was administered intrathecally or intravesically in normal rats or rats pretreated with capsaicin. The effects of intravenous injection of the selective ETA receptor antagonist ABT-627, or selective ETB receptor antagonist A-192621 (Abbott Laboratories, Abbott Park, Illinois) intrathecal injection of the opioid receptor antagonist naloxone hydrochloride on changes in bladder activity induced by intravesical or intrathecal ET-1 administration were investigated. Results: Intravesical injection of ET-1 (0.1 to 10 μM) induced detrusor overactivity, as evidenced by a decrease in intercontraction intervals, in a dose dependent manner. ET-1 induced detrusor overactivity was suppressed by intravenous application of ABT-627 (0.1 mg/kg) as well as capsaicin pretreatment but not by A-192621. In contrast, intrathecal injection of ET-1 (0.5 to 50 fmol) increased intercontraction intervals dose dependently and ET-1 at a higher dose (50 fmol) induced urinary retention. These inhibitory effects were antagonized by ABT-627 (10 mg/kg) and also by intrathecal application of naloxone but not by A-192621. Conclusions: These results indicate that the activation of ETA receptors in capsaicin sensitive C-fiber afferents in the bladder can induce detrusor overactivity, while ETA receptor activation in the spinal cord can inhibit the micturition reflex via activation of a spinal opioid mechanism. Thus, targeting peripheral ETA receptors could be an effective treatment for bladder overactivity and/or painful conditions.

Original languageEnglish (US)
Pages (from-to)1533-1537
Number of pages5
JournalJournal of Urology
Volume172
Issue number4 I
DOIs
StatePublished - Oct 2004
Externally publishedYes

Fingerprint

Endothelin Receptors
Urination
Endothelin-1
A 192621
Reflex
Urinary Bladder
Spinal Injections
Capsaicin
Naloxone
Spinal Cord
Intravesical Administration
TRPV Cation Channels
Unmyelinated Nerve Fibers
Urinary Retention
Narcotic Antagonists
Urethane
Intravenous Injections
Opioid Analgesics
atrasentan

Keywords

  • Bladder
  • Capsaicin
  • Endothelins
  • Receptors, opioid
  • Spinal cord

ASJC Scopus subject areas

  • Urology

Cite this

Differential roles of peripheral and spinal endothelin receptors in the micturition reflex in rats. / Ogawa, Teruyuki; Kamo, Izumi; Pflug, Beth; Nelson, Joel B.; Seki, Satoshi; Igawa, Yasuhiko; Nishizawa, Osamu; De Groat, William C.; Chancellor, Michael B.; Yoshimura, Naoki.

In: Journal of Urology, Vol. 172, No. 4 I, 10.2004, p. 1533-1537.

Research output: Contribution to journalArticle

Ogawa, T, Kamo, I, Pflug, B, Nelson, JB, Seki, S, Igawa, Y, Nishizawa, O, De Groat, WC, Chancellor, MB & Yoshimura, N 2004, 'Differential roles of peripheral and spinal endothelin receptors in the micturition reflex in rats', Journal of Urology, vol. 172, no. 4 I, pp. 1533-1537. https://doi.org/10.1097/01.ju.0000139540.56916.0e
Ogawa, Teruyuki ; Kamo, Izumi ; Pflug, Beth ; Nelson, Joel B. ; Seki, Satoshi ; Igawa, Yasuhiko ; Nishizawa, Osamu ; De Groat, William C. ; Chancellor, Michael B. ; Yoshimura, Naoki. / Differential roles of peripheral and spinal endothelin receptors in the micturition reflex in rats. In: Journal of Urology. 2004 ; Vol. 172, No. 4 I. pp. 1533-1537.
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AU - Kamo, Izumi

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AU - Seki, Satoshi

AU - Igawa, Yasuhiko

AU - Nishizawa, Osamu

AU - De Groat, William C.

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