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Am J Physiol Regul Integr Comp Physiol (February 9, 2006). doi:10.1152/ajpregu.00780.2005
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Submitted on November 3, 2005
Accepted on February 1, 2006

Roles of Glutamatergic and Serotonergic Mechanisms in Reflex Control of the External Urethral Sphincter in Urethane-anesthetized Female Rats

Hui-Yi Chang1, Chen-Li Cheng2, Jia-Jin J Chen3*, and William C de Groat4

1 National Cheng Kung University, Institute of Biomedical Engineering, Tainan, Taiwan; University of Pittsburgh School of Medicine, Department of Pharmacology, Pittsburgh, PA, USA
2 Taichung Veterans General Hospital, Division of Urology, Department of Surgery, Taichung, Taiwan
3 National Cheng Kung University, Institute of Biomedical Engineering, Tainan, Taiwan
4 University of Pittsburgh School of Medicine, Department of Pharmacology, Pittsburgh, PA, USA

* To whom correspondence should be addressed. E-mail: jason{at}jason.bme.ncku.edu.tw.

This study was conducted to examine reflex mechanisms that mediate urinary bladder and external urethral sphincter (EUS) coordination in urethane-anesthetized female Sprague-Dawley rats. We examined the properties of EUS reflexes elicited by electrical stimulation of pelvic nerve afferent axons (pelvic-EUS reflex). The changes in the reflexes induced by bladder distension and by administration of agonists or antagonists for glutamatergic or serotonergic receptors were examined. The reflexes consisted of an early response (ER, latency, 18-22 ms) and a late, long duration response (LR, latency greater than 100 ms) that consisted of bursts of activity at 20-160 ms inter-burst intervals. In a few experiments a reflex with an intermediate latency (40-70 ms) was also identified. With the bladder empty the ER was present but the LR was not detected in the majority of experiments. The LR was markedly enhanced when the bladder was distended. The ER remained but the LR was abolished after transection of the spinal cord at the T8-9 level. The ER and LR were significantly decreased 75% and 35%, respectively, by an NMDA receptor antagonist (MK801, 0.3 mg/kg, i.v.), but only decreased 18% and 14%, respectively, by an AMPA receptor antagonist (LY215490, 3 mg/kg, i.v.). A 5-HT1A receptor agonist (8-OH-DPAT, 1 mg/kg, i.v.) enhanced spontaneous EUS activity and the pelvic-EUS reflexes. WAY100635 (0.1-1 mg/kg, i.v.), a 5-HT1A antagonist, reversed the effect of 8-OH-DPAT and suppressed EUS activity and the pelvic-EUS reflex. These results indicate that glutamatergic and serotonergic mechanisms are important in the reflex pathways underlying bladder-sphincter coordination in rats.




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