Dept. of Urology, Univ. of Pittsburgh, 700 Kaufmann Bldg., Pittsburgh, PA 15213.
Am J Physiol Renal Physiol. 2014 Apr 1;306(7):F781-9. doi: 10.1152/ajprenal.00679.2013. Epub 2014 Feb 12.
Picrotoxin, an antagonist for γ-aminobutyric acid receptor subtype A (GABAA), was used to investigate the role of GABAA receptors in nociceptive and nonnociceptive reflex bladder activities and pudendal inhibition of these activities in cats under α-chloralose anesthesia. Acetic acid (AA; 0.25%) was used to irritate the bladder and induce nociceptive bladder overactivity, while saline was used to distend the bladder and induce nonnociceptive bladder activity. To modulate the bladder reflex, pudendal nerve stimulation (PNS) was applied at multiple threshold (T) intensities for inducing anal sphincter twitching. AA irritation significantly (P < 0.01) reduced bladder capacity to 34.3 ± 7.1% of the saline control capacity, while PNS at 2T and 4T significantly (P < 0.01) increased AA bladder capacity to 84.0 ± 7.8 and 93.2 ± 15.0%, respectively, of the saline control. Picrotoxin (0.4 mg it) did not change AA bladder capacity but completely removed PNS inhibition of AA-induced bladder overactivity. Picrotoxin (iv) only increased AA bladder capacity at a high dose (0.3 mg/kg) but significantly (P < 0.05) reduced 2T PNS inhibition at low doses (0.01-0.1 mg/kg). During saline cystometry, PNS significantly (P < 0.01) increased bladder capacity to 147.0 ± 7.6% at 2T and 172.7 ± 8.9% at 4T of control capacity, and picrotoxin (0.4 mg it or 0.03-0.3 mg/kg iv) also significantly (P < 0.05) increased bladder capacity. However, picrotoxin treatment did not alter PNS inhibition during saline infusion. These results indicate that spinal GABAA receptors have different roles in controlling nociceptive and nonnociceptive reflex bladder activities and in PNS inhibition of these activities.
胡椒碱，一种 γ-氨基丁酸受体亚型 A（GABAA）拮抗剂，被用于研究 GABAA 受体在猫麻醉下的伤害性和非伤害性反射膀胱活动以及阴部抑制这些活动中的作用。醋酸（AA；0.25%）用于刺激膀胱并引起伤害性膀胱过度活动，而盐水用于扩张膀胱并引起非伤害性膀胱活动。为了调节膀胱反射，阴部神经刺激（PNS）应用于多个阈值（T）强度以诱导肛门括约肌抽搐。AA 刺激显著（P < 0.01）将膀胱容量降低至盐水对照容量的 34.3 ± 7.1%，而 2T 和 4T 的 PNS 显著（P < 0.01）将 AA 膀胱容量增加至盐水对照容量的 84.0 ± 7.8%和 93.2 ± 15.0%。胡椒碱（0.4 mg iv）不改变 AA 膀胱容量，但完全消除了 PNS 对 AA 诱导的膀胱过度活动的抑制作用。胡椒碱（iv）仅在高剂量（0.3 mg/kg）时增加 AA 膀胱容量，但在低剂量（0.01-0.1 mg/kg）时显著（P < 0.05）降低 2T PNS 抑制作用。在盐水膀胱测压期间，PNS 显著（P < 0.01）将膀胱容量增加至对照容量的 147.0 ± 7.6%（2T）和 172.7 ± 8.9%（4T），而胡椒碱（0.4 mg iv 或 0.03-0.3 mg/kg iv）也显著（P < 0.05）增加了膀胱容量。然而，胡椒碱处理并未改变盐水输注期间 PNS 抑制作用。这些结果表明，脊髓 GABAA 受体在控制伤害性和非伤害性反射膀胱活动以及 PNS 抑制这些活动方面具有不同的作用。
