Effect of 5-Hydroxytryptamine1 Serotonin Receptor Agonists on Noxiously Stimulated Micturition in Cats With Chronic Spinal Cord Injury

Baojun Gu, Karl B. Thor, Jerome P. Reiter, Paul C. Dolber

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Purpose: The serotonin 5-hydroxytryptamine1A/7 receptor agonist (R)-8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)tetralin) (Sigma®) and the 5-hydroxytryptamine1A/1B/1D agonist GR-46611 (3-[3-(2-dimethylaminoethyl)-1H-indol-5-yl]-N-(4-methoxybenzyl)acrylamide) (Tocris Cookson, Ellisville, Missouri) inhibit bladder activity during saline infusion into the bladder of cats with chronic spinal cord injury (saline infused, spinal cord injured cats), suggesting an effect on mechanosensitive bladder afferent C fibers or their targets. We investigated the effects of (R)-8-OH-DPAT and GR-46611 on bladder activity in chronic spinal cord injured cats during infusion of dilute acetic acid into the bladder to stimulate chemosensitive bladder afferent C fibers (acid infused, spinal cord injured cats). Materials and Methods: Chloralose anesthetized, spinal cord injured cats were catheterized through the bladder dome for filling cystometry during 0.5% acetic acid infusion. Dose-response curves for (R)-8-OH-DPAT (0.3 to 30 μg/kg intravenously) or GR-46611 (0.03 to 300 μg/kg intravenously) were followed by the 5-hydroxytryptamine1A antagonist WAY-100635 (N-tert-butyl-3-(4-(2-methoxyphenyl)-piperazin-1-yl)-2-phenylpropanamide) (Sigma) (300 μg/kg). Threshold volume, bladder capacity, residual volume, micturition volume and arterial pressure were measured and external urethral sphincter electromyogram was recorded. Results: Acid infused, spinal cord injured cats responded to (R)-8-OH-DPAT but not to GR-46611 with dose dependent increases in threshold volume, capacity and residual volume (significant above 3 μg/kg). Effects of (R)-8-OH-DPAT were largely reversed by WAY-100635. Neither (R)-8-OH-DPAT nor GR-46611 augmented external urethral sphincter electromyogram activity. Conclusions: Based on differences in the response to GR-46611 in saline vs acid infused, spinal cord injured animals it is tempting to speculate that 2 distinct populations of bladder afferent C fibers (1 chemosensitive and 1 mechanosensitive) can initiate spinal bladder reflexes. Because 5-hydroxytryptamine1A receptor agonists increased bladder capacity under saline or acid infused conditions, they are promising candidates for decreasing bladder hyperactivity and increasing bladder capacity in patients with chronic spinal cord injury.

Original languageEnglish (US)
Pages (from-to)2381-2385
Number of pages5
JournalJournal of Urology
Volume177
Issue number6
DOIs
StatePublished - Jun 2007
Externally publishedYes

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Serotonin Receptor Agonists
Urination
Spinal Cord Injuries
Urinary Bladder
Cats
8-Hydroxy-2-(di-n-propylamino)tetralin
Spinal Cord
Unmyelinated Nerve Fibers
Residual Volume
Acids
Electromyography
Urethra
Acetic Acid
Chloralose
Acrylamide
Reflex
GR 46611
hydroxide ion
Serotonin
Arterial Pressure

Keywords

  • bladder
  • cats
  • receptors
  • serotonin
  • spinal cord injuries
  • urination

ASJC Scopus subject areas

  • Urology

Cite this

Effect of 5-Hydroxytryptamine1 Serotonin Receptor Agonists on Noxiously Stimulated Micturition in Cats With Chronic Spinal Cord Injury. / Gu, Baojun; Thor, Karl B.; Reiter, Jerome P.; Dolber, Paul C.

In: Journal of Urology, Vol. 177, No. 6, 06.2007, p. 2381-2385.

Research output: Contribution to journalArticle

Gu, Baojun ; Thor, Karl B. ; Reiter, Jerome P. ; Dolber, Paul C. / Effect of 5-Hydroxytryptamine1 Serotonin Receptor Agonists on Noxiously Stimulated Micturition in Cats With Chronic Spinal Cord Injury. In: Journal of Urology. 2007 ; Vol. 177, No. 6. pp. 2381-2385.
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abstract = "Purpose: The serotonin 5-hydroxytryptamine1A/7 receptor agonist (R)-8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)tetralin) (Sigma{\circledR}) and the 5-hydroxytryptamine1A/1B/1D agonist GR-46611 (3-[3-(2-dimethylaminoethyl)-1H-indol-5-yl]-N-(4-methoxybenzyl)acrylamide) (Tocris Cookson, Ellisville, Missouri) inhibit bladder activity during saline infusion into the bladder of cats with chronic spinal cord injury (saline infused, spinal cord injured cats), suggesting an effect on mechanosensitive bladder afferent C fibers or their targets. We investigated the effects of (R)-8-OH-DPAT and GR-46611 on bladder activity in chronic spinal cord injured cats during infusion of dilute acetic acid into the bladder to stimulate chemosensitive bladder afferent C fibers (acid infused, spinal cord injured cats). Materials and Methods: Chloralose anesthetized, spinal cord injured cats were catheterized through the bladder dome for filling cystometry during 0.5{\%} acetic acid infusion. Dose-response curves for (R)-8-OH-DPAT (0.3 to 30 μg/kg intravenously) or GR-46611 (0.03 to 300 μg/kg intravenously) were followed by the 5-hydroxytryptamine1A antagonist WAY-100635 (N-tert-butyl-3-(4-(2-methoxyphenyl)-piperazin-1-yl)-2-phenylpropanamide) (Sigma) (300 μg/kg). Threshold volume, bladder capacity, residual volume, micturition volume and arterial pressure were measured and external urethral sphincter electromyogram was recorded. Results: Acid infused, spinal cord injured cats responded to (R)-8-OH-DPAT but not to GR-46611 with dose dependent increases in threshold volume, capacity and residual volume (significant above 3 μg/kg). Effects of (R)-8-OH-DPAT were largely reversed by WAY-100635. Neither (R)-8-OH-DPAT nor GR-46611 augmented external urethral sphincter electromyogram activity. Conclusions: Based on differences in the response to GR-46611 in saline vs acid infused, spinal cord injured animals it is tempting to speculate that 2 distinct populations of bladder afferent C fibers (1 chemosensitive and 1 mechanosensitive) can initiate spinal bladder reflexes. Because 5-hydroxytryptamine1A receptor agonists increased bladder capacity under saline or acid infused conditions, they are promising candidates for decreasing bladder hyperactivity and increasing bladder capacity in patients with chronic spinal cord injury.",
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AU - Thor, Karl B.

AU - Reiter, Jerome P.

AU - Dolber, Paul C.

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N2 - Purpose: The serotonin 5-hydroxytryptamine1A/7 receptor agonist (R)-8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)tetralin) (Sigma®) and the 5-hydroxytryptamine1A/1B/1D agonist GR-46611 (3-[3-(2-dimethylaminoethyl)-1H-indol-5-yl]-N-(4-methoxybenzyl)acrylamide) (Tocris Cookson, Ellisville, Missouri) inhibit bladder activity during saline infusion into the bladder of cats with chronic spinal cord injury (saline infused, spinal cord injured cats), suggesting an effect on mechanosensitive bladder afferent C fibers or their targets. We investigated the effects of (R)-8-OH-DPAT and GR-46611 on bladder activity in chronic spinal cord injured cats during infusion of dilute acetic acid into the bladder to stimulate chemosensitive bladder afferent C fibers (acid infused, spinal cord injured cats). Materials and Methods: Chloralose anesthetized, spinal cord injured cats were catheterized through the bladder dome for filling cystometry during 0.5% acetic acid infusion. Dose-response curves for (R)-8-OH-DPAT (0.3 to 30 μg/kg intravenously) or GR-46611 (0.03 to 300 μg/kg intravenously) were followed by the 5-hydroxytryptamine1A antagonist WAY-100635 (N-tert-butyl-3-(4-(2-methoxyphenyl)-piperazin-1-yl)-2-phenylpropanamide) (Sigma) (300 μg/kg). Threshold volume, bladder capacity, residual volume, micturition volume and arterial pressure were measured and external urethral sphincter electromyogram was recorded. Results: Acid infused, spinal cord injured cats responded to (R)-8-OH-DPAT but not to GR-46611 with dose dependent increases in threshold volume, capacity and residual volume (significant above 3 μg/kg). Effects of (R)-8-OH-DPAT were largely reversed by WAY-100635. Neither (R)-8-OH-DPAT nor GR-46611 augmented external urethral sphincter electromyogram activity. Conclusions: Based on differences in the response to GR-46611 in saline vs acid infused, spinal cord injured animals it is tempting to speculate that 2 distinct populations of bladder afferent C fibers (1 chemosensitive and 1 mechanosensitive) can initiate spinal bladder reflexes. Because 5-hydroxytryptamine1A receptor agonists increased bladder capacity under saline or acid infused conditions, they are promising candidates for decreasing bladder hyperactivity and increasing bladder capacity in patients with chronic spinal cord injury.

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KW - cats

KW - receptors

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KW - spinal cord injuries

KW - urination

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