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, Paul C. Dolber

Research output: Contribution to journalArticle

21 Citations (Scopus)

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 β3 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.

Original languageEnglish (US)
Pages (from-to)1266-1272
Number of pages7
JournalJournal of Pharmacology and Experimental Therapeutics
Volume310
Issue number3
DOIs
StatePublished - Sep 2004
Externally publishedYes

Fingerprint

8-Hydroxy-2-(di-n-propylamino)tetralin
Serotonin Receptor Agonists
Spinal Cord Injuries
Urinary Bladder
Cats
Urination
Serotonin 5-HT1 Receptor Agonists
Unmyelinated Nerve Fibers
Receptor, Serotonin, 5-HT1A
Residual Volume
Receptor, Serotonin, 5-HT1D
Serotonin 5-HT1 Receptor Antagonists
Chloralose
Acrylamide
Inhibition (Psychology)
Reflex
hydroxide ion
Serotonin
Spinal Cord
Arterial Pressure

ASJC Scopus subject areas

  • Pharmacology

Cite this

Inhibition of bladder activity by 5-hydroxytryptamine1 serotonin receptor agonists in cats with chronic spinal cord injury. / Gu, Baojun; Olejar, Kenneth J.; Reiter, Jerome P.; Thor, Karl B.; Dolber, Paul C.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 310, No. 3, 09.2004, p. 1266-1272.

Research output: Contribution to journalArticle

Gu, Baojun ; Olejar, Kenneth J. ; Reiter, Jerome P. ; Thor, Karl B. ; Dolber, Paul C. / Inhibition of bladder activity by 5-hydroxytryptamine1 serotonin receptor agonists in cats with chronic spinal cord injury. In: Journal of Pharmacology and Experimental Therapeutics. 2004 ; Vol. 310, No. 3. pp. 1266-1272.
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