Acute anal stretch inhibits NMDA-dependent pelvic-urethra reflex potentiation via spinal GABAergic inhibition in anesthetized rats.
The impact of acute anal stretch on the pelvic-urethra reflex potentiation was examined in urethane-anesthetized rats by recording the external urethra sphincter electromyogram activity evoked by the pelvic afferent stimulation. Test stimulation (1 stimulation/30 s) evoked a baseline reflex activity with a single action potential that was abolished by gallamine (5 mg/kg iv). On the other hand, the repetitive stimulation (1 stimulation/1 s) induced spinal reflex potentiation (SRP) that was attenuated by intrathecal 6-cyano-7-nitroquinoxaline-2,4-dione (a glutamatergic alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionat receptor antagonist, 100 microM, 10 microl) and d-2-amino-5-phosphonovalerate [a glutamatergic N-methyl-D-aspartate (NMDA) antagonist, 100 microM, 10 microl]. Acute anal stretch using a mosquito clamp with a distance of 4 mm exhibited no effect, whereas distances of 8 mm attenuated and 12 mm abolished the repetitive stimulation-induced SRP. Intrathecal NMDA (100 microM, 10 microl) reversed the abolition on SRP caused by anal stretch. On the other hand, pretreated bicuculline [gamma-aminobutyric acid (GABA) A receptor antagonist, 100 microM, 10 microl] but not hydroxysaclofen (GABAB receptor antagonist) counteracted the abolition on the repetitive stimulation-induced SRP caused by the anal stretch. All of the results suggested that anal stretch may be used as an adjunct to assist voiding dysfunction in patients with overactive urethra sphincter and that GABAergic neurotransmission is important in the neural mechanisms underlying external urethra sphincter activity inhibited by anal stretch.
Chen
Sung-Lang
SL
Department of Urology, Chung-Shan Medical University Hospital, and Department of Physiology, College of Medicine, Chung-Shan Medical University, #110, Chien-Kuo North Rd. 1st Section Taichung, Taiwan 10018.
Huang
Yu-Hui
YH
Kao
Yu-Lin
YL
Chen
Gin-Den
GD
Cheng
Chen-Li
CL
Peng
Hsien-Yu
HY
Liao
Jiuan-Miaw
JM
Huang
Pei-Chen
PC
Tsai
Shih-Jei
SJ
Lin
Tzer-Bin
TB
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D001003:Anal Canal / Q000294:innervation* / Q000502:physiology; D000758:Anesthesia; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D004558:Electric Stimulation; D004576:Electromyography; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D018756:GABA Antagonists / Q000494:pharmacology; D005703:Gallamine Triethiodide / Q000494:pharmacology; D016202:N-Methylaspartate / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D009433:Neural Inhibition / Q000502:physiology*; D003473:Neuromuscular Nondepolarizing Agents / Q000494:pharmacology; D010388:Pelvis / Q000294:innervation; D051381:Rats; D017208:Rats, Wistar; D012018:Reflex / Q000187:drug effects / Q000502:physiology*; D013116:Spinal Cord / Q000502:physiology; D014521:Urethra / Q000294:innervation* / Q000502:physiology; D014554:Urination / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D003473:Neuromuscular Nondepolarizing Agents; D005680:gamma-Aminobutyric Acid; D016202:N-Methylaspartate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D015763:2-Amino-5-phosphonovalerate; D005703:Gallamine Triethiodide; D001640:Bicuculline