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Research ArticleGASTROINTESTINAL, HEPATIC, PULMONARY, AND RENAL

Inhibition of Bladder Activity by 5-Hydroxytryptamine1 Serotonin Receptor Agonists in Cats with Chronic Spinal Cord Injury

Baojun Gu, Kenneth J. Olejar, Jerome P. Reiter, Karl B. Thor and Paul C. Dolber
Journal of Pharmacology and Experimental Therapeutics September 2004, 310 (3) 1266-1272; DOI: https://doi.org/10.1124/jpet.103.063842
Baojun Gu
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Kenneth J. Olejar
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Jerome P. Reiter
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Karl B. Thor
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Paul C. Dolber
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Abstract

The serotonin (5-hydroxytryptamine1A) 5-HT1A receptor agonist 8-OH-DPAT [(R)- (+)-8-hydroxy-2-(di-n-propylamino)tetralin] inhibits bladder activity under nociceptive but not innocuous conditions in cats with an intact spinal cord, suggestive of an effect on primary afferent C fibers or their targets. Because C fibers play a key role in reflex micturition in chronic spinal cord injury (SCI), we investigated the effect of 8-OH-DPAT on micturition in SCI cats. We also investigated GR-46611 (3-[3-(2-dimethylaminoethyl)-1H-indol-5-yl]-N-(4-methoxybenzyl)acrylamide), which has agonist activity predominantly at 5-HT1B and 5-HT1D receptors but also at the 5-HT1A receptor. Chloralose-anesthetized cats were catheterized through the bladder dome for saline-filling cystometry. Dose-response curves for i.v. 8-OH-DPAT (0.3-30 μg/kg) and GR-46611 (0.03-300 μg/kg) were followed in three cases each by 5-HT1A antagonist WAY-100635 [N-tert-butyl-3-(4-(2-methoxyphenyl)-piperazin-1-yl)-2-phenylpropanamide] at 300 μg/kg. Threshold volume, capacity, residual volume, micturition volume, and arterial pressure were measured. Intact cats showed few significant changes in cystometric variables. SCI cats responded to both 8-OH-DPAT and GR-46611 with dose-dependent increases in threshold volume, capacity, and residual volume, significant at ≥10 μg/kg for 8-OH-DPAT and at ≥3 μg/kg for GR-46611. Effects of 8-OH-DPAT but not GR-46611 were largely reversed by WAY-100635. Both 5-HT1A and 5-HT1B/1D agonists may offer a promising means of reducing bladder hyperactivity and increasing bladder capacity in patients with chronic SCI.

Footnotes

  • Supported by a Veterans Affairs Merit Review Award and a grant from the Christopher Reeve Paralysis Foundation.

  • doi:10.1124/jpet.103.063842.

  • ABBREVIATIONS. SCI, spinal cord injury; EUS, external urethral sphincter; 5-HT1, 5-hydroxytryptamine1; EMG, electromyogram; 8-OH-DPAT, (R)-(+)-8-hydroxy-2-(di-n-propylamino)tetralin; GR-46611, 3-[3-(2-dimethylaminoethyl)-1H-indol-5-yl]-N-(4-methoxybenzyl)acrylamide; WAY-100635, N-tert-butyl-3-(4-(2-methoxyphenyl)-piperazin-1-yl)-2-phenylpropanamide.

    • Received February 12, 2004.
    • Accepted May 19, 2004.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 310 (3)
Journal of Pharmacology and Experimental Therapeutics
Vol. 310, Issue 3
1 Sep 2004
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Research ArticleGASTROINTESTINAL, HEPATIC, PULMONARY, AND RENAL

Inhibition of Bladder Activity by 5-Hydroxytryptamine1 Serotonin Receptor Agonists in Cats with Chronic Spinal Cord Injury

Baojun Gu, Kenneth J. Olejar, Jerome P. Reiter, Karl B. Thor and Paul C. Dolber
Journal of Pharmacology and Experimental Therapeutics September 1, 2004, 310 (3) 1266-1272; DOI: https://doi.org/10.1124/jpet.103.063842

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Research ArticleGASTROINTESTINAL, HEPATIC, PULMONARY, AND RENAL

Inhibition of Bladder Activity by 5-Hydroxytryptamine1 Serotonin Receptor Agonists in Cats with Chronic Spinal Cord Injury

Baojun Gu, Kenneth J. Olejar, Jerome P. Reiter, Karl B. Thor and Paul C. Dolber
Journal of Pharmacology and Experimental Therapeutics September 1, 2004, 310 (3) 1266-1272; DOI: https://doi.org/10.1124/jpet.103.063842
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