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Am J Physiol Regul Integr Comp Physiol 280: R1407-R1413, 2001;
0363-6119/01 $5.00
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Vol. 280, Issue 5, R1407-R1413, May 2001

Effects of WAY100635, a selective 5-HT1A-receptor antagonist on the micturition-reflex pathway in the rat

Hidehiro Kakizaki, Mitsuharu Yoshiyama, Tomohiko Koyanagi, and William C. De Groat

Department of Pharmacology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261; and Department of Urology, Hokkaido University Graduate School of Medicine, Sapporo, 060 - 8638, Japan

5-Hydroxytryptamine (5-HT) receptors in the central nervous system have been implicated in the control of micturition. The present study was undertaken to evaluate the effects of a selective 5-HT1A-receptor antagonist {N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cyclohexanecarboxamide trihydrochloride (WAY100635)} on the micturition-reflex pathway in urethane-anesthetized female Wistar rats. Rhythmic isovolumetric bladder contractions evoked by bladder distension were abolished by 0.3- to 3-mg/kg iv or 30- to 100-µg intrathecal (it) administration of WAY100635 in a dose-dependent manner for periods of 3-15 min. Intrathecal injection of WAY100635 was effective only if injected at the L6-S1 spinal cord level, but not at the thoracic or cervical cord levels. WAY100635 (30-100 µg it) significantly reduced the amplitude of bladder contractions evoked by electrical stimulation of the pontine micturition center. However, the field potentials in the rostral pons evoked by electrical stimulation of pelvic nerve were not affected by intrathecal or intravenous injection of WAY100635. These results suggest that 5-HT1A receptors at the L6-S1 level of the spinal cord have an important role in the tonic control of the descending limb of the micturition-reflex pathway in the rat.

5-hydroxytryptamine receptor; spinal cord; pontine micturition center; pelvic nerve; bladder


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