Role of 5-HT1A receptors in control of lower urinary tract function in anesthetized rats.
The role of 5-hydroxytryptamine (5-HT) 1A (5-HT1A) receptors in lower urinary tract function was examined in urethane-anesthetized female Sprague-Dawley rats. Bladder pressure and the external urethral sphincter electromyogram (EUS EMG) activity were recorded during continuous-infusion transvesical cystometrograms (TV-CMGs) to allow voiding and during transurethral-CMGs (TU-CMGs) which prevented voiding and allowed recording of isovolumetric bladder contractions. 8-Hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT), a 5-HT1A receptor agonist, decreased volume threshold (VT) for initiating voiding and increased contraction amplitude (CA) during TU-CMGs but decreased CA during TV-CMGs. 8-OH-DPAT prolonged EUS bursting as well as the intrabursting silent periods (SP) during voiding. N-[2-[4-(2-methoxyphenyl)-1- piperazinyl]ethyl]-N-(2-pyridinyl)cyclohexanecarboxamine trihydrochloride (WAY-100635), a 5-HT1A antagonist, increased VT, increased residual volume, markedly decreased voiding efficiency, decreased the amplitude of micturition contractions recorded under isovolumetric conditions, and decreased the SP of EUS bursting. These results indicate that activation of 5-HT1A receptors by endogenous 5-HT lowers the threshold for initiating reflex voiding and promotes voiding function by enhancing the duration of EUS relaxation, which should reduce urethral outlet resistance.
Cheng
Chen-Li
CL
Division of Urology, Department of Surgery, Taichung Veterans General Hospital, Taichung, Taiwan, ROC. cheng20011@gmail.com
de Groat
William C
WC
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000768:Anesthesia, General; D000818:Animals; D004576:Electromyography; D005260:Female; D009119:Muscle Contraction / Q000187:drug effects; D003473:Neuromuscular Nondepolarizing Agents / Q000494:pharmacology; D010197:Pancuronium / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011312:Pressure; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D012018:Reflex; D012701:Serotonin / Q000378:metabolism*; D058825:Serotonin 5-HT1 Receptor Agonists; D058829:Serotonin 5-HT1 Receptor Antagonists; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013997:Time Factors; D001743:Urinary Bladder / Q000187:drug effects / Q000294:innervation / Q000378:metabolism*; D014554:Urination / Q000187:drug effects
D003473:Neuromuscular Nondepolarizing Agents; D010879:Piperazines; D011725:Pyridines; D058825:Serotonin 5-HT1 Receptor Agonists; D058829:Serotonin 5-HT1 Receptor Antagonists; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D044282:Receptor, Serotonin, 5-HT1A; D012701:Serotonin; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D010197:Pancuronium