Thor Karl B, Katofiasc Mary A, Danuser Hansjorg, Springer Johannes, Schaus John M
Division of Nervous System Disorders, Eli Lilly and Co., Indianapolis, IN, USA.
Brain Res. 2002 Aug 16;946(2):290-7. doi: 10.1016/s0006-8993(02)02897-4.
In the present study, the role of 5-HT(1A) receptors in control of lower urinary tract function in cats was examined using 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) as agonists and WAY100635 and LY206130 as antagonists. Bladder function was assessed using cystometric infusion of saline or 0.5% acetic acid to produce bladder irritation. External urethral sphincter (EUS) function was assessed using electromyographic (EMG) recordings of activity recorded during cystometry or by recording electrically evoked pudendal reflexes. Both 5-HT(1A) receptor agonists caused dose-dependent decreases in bladder activity and increases in EUS EMG activity under conditions of acetic acid infusion. 5-HT(1A) receptor antagonists reversed both the bladder-inhibitory and sphincter-facilitatory effects. Thus, 5-HT(1A) receptor activation can have opposite effects on nociceptive afferent processing depending upon the efferent response being measured. During saline infusion of the bladder, 8-OH-DPAT produced moderate inhibition of bladder activity and had no significant effect on sphincter electromyographic (EMG) activity. 8-OH-DPAT either had no effect, or inhibited, low-threshold electrically evoked pudendal reflexes. These findings indicate that 5-HT(1A) receptor stimulation is inhibitory to bladder function in cats, especially under conditions where the bladder is hyperactive due to irritation. Furthermore, these bladder-inhibitory effects are the exact opposite of the bladder-excitatory effects of 8-OH-DPAT reported in rats. 5-HT(1A) receptor stimulation increases EUS motoneuron activity when driven by nociceptive bladder afferent inputs but not when driven by non-nociceptive afferent inputs. In summary, 5-HT(1A) receptor agonists facilitate a nociceptor-driven spinal reflex (sphincter activity) but inhibit a nociceptor-driven supraspinal reflex (micturition). This pattern of activity would facilitate urine storage and may be important under 'fight-or-flight' conditions when serotonergic activity is high.
在本研究中，使用8-羟基-2-（二正丙基氨基）四氢萘（8-OH-DPAT）和5-甲氧基-N，N-二甲基色胺（5-MeODMT）作为激动剂，WAY100635和LY206130作为拮抗剂，研究了5-HT(1A)受体在猫下尿路功能控制中的作用。通过膀胱内注入生理盐水或0.5%醋酸以产生膀胱刺激来评估膀胱功能。通过膀胱测压期间记录的肌电图（EMG）活动或通过记录电诱发的阴部反射来评估尿道外括约肌（EUS）功能。在注入醋酸的情况下，两种5-HT(1A)受体激动剂均导致膀胱活动呈剂量依赖性降低，EUS肌电图活动增加。5-HT(1A)受体拮抗剂可逆转膀胱抑制和括约肌促进作用。因此，5-HT(1A)受体激活对伤害性传入处理可产生相反的作用，这取决于所测量的传出反应。在膀胱注入生理盐水期间，8-OH-DPAT对膀胱活动产生中度抑制，对括约肌肌电图（EMG）活动无显著影响。8-OH-DPAT对低阈值电诱发的阴部反射要么没有影响，要么起抑制作用。这些发现表明，5-HT(1A)受体刺激对猫的膀胱功能具有抑制作用，尤其是在膀胱因刺激而活动亢进的情况下。此外，这些膀胱抑制作用与大鼠中报道的8-OH-DPAT的膀胱兴奋作用正好相反。当由伤害性膀胱传入输入驱动时，5-HT(1A)受体刺激会增加EUS运动神经元活动，但由非伤害性传入输入驱动时则不会。总之，5-HT(1A)受体激动剂促进伤害感受器驱动的脊髓反射（括约肌活动），但抑制伤害感受器驱动的脊髓上反射（排尿）。这种活动模式将有助于尿液储存，并且在血清素能活动较高的“战斗或逃跑”条件下可能很重要。
