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1 Institute of Biomedical Engineering, National Cheng Kung University, Tainan, Taiwan - Republic of China; Department of Pharmacology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States
2 Division of Urology, Department of Surgery, Taichung Veterans General Hospital, Taichung, Taiwan - Republic of China
3 Institute of Biomedical Engineering, National Cheng Kung University, Tainan, Taiwan - Republic of China
4 Department of Pharmacology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States
* To whom correspondence should be addressed. E-mail: degroat{at}pharm.server.pitt.edu.
Lower urinary tract function is regulated by spinal and supraspinal reflexes that coordinate the activity of the urinary bladder and external urethral sphincter (EUS). Two types of EUS activity (tonic and bursting) have been identified in rats. This study in urethane-anesthetized female rats used cystometry, EUS electromyography, spinal cord transection (SCT) at different segmental levels and analysis of the effects of 5-HT1A receptor agonist (8-OH-DPAT) and antagonist (WAY100635) drugs to examine the origin of tonic and bursting EUS activity. EUS activity was elicited by bladder distension or electrical stimulation of afferent axons in the pelvic nerve (pelvic-EUS reflex). Tonic activity evoked by bladder distension was detected in spinal cord intact rats and after acute and chronic T8-9 or L3-4 SCT, but was abolished after L6-S1 SCT. Bursting activity was abolished by all types of SCT except chronic T8-9 transection. 8-OH-DPAT enhanced tonic activity and WAY100635 reversed the effect of 8-OH-DPAT. The pelvic-EUS reflex consisted of an early response (ER) and late response (LR) when the bladder was distended in spinal cord intact rats. ER remained after acute or chronic T8-9 and L3-4 SCT, but was absent after L6-S1 SCT. LR occurred only in chronic T8-9 SCT rats where it was enhanced or unmasked by 8-OH-DPAT. The results indicate that spinal serotonergic mechanisms facilitate tonic and bursting EUS activity. The circuitry for generating different patterns of EUS activity appears to be located in different segments of the spinal cord: tonic activity at L6-S1 and bursting activity between T8-9 and L3-4.
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