Yıldırım Şeniz, Öztürk Fincan Gökçe Sevim, İşli Fatma, Ercan Sevim, Sarıoğlu Yusuf
Department of Medical Pharmacology, Kırıkkale University, Kırıkkale, Turkey.
Department of Medical Pharmacology, Gazi University, Ankara, Turkey.
Pharmacol Rep. 2016 Oct;68(5):926-34. doi: 10.1016/j.pharep.2016.04.012. Epub 2016 May 3.
Dopamine is a crucial central neurotransmitter that plays a fundamental role in the autonomic and somatic components of penile reflexes in animals and humans. Similar to the erectile responses of dopamine, systemic administration of l-DOPA induces yawning and penile erection in some species. The possible effects of l-DOPA on nitric oxide (NO)-dependent and -independent non-adrenergic non-cholinergic (NANC) relaxation responses mediated by electrical field stimulation (EFS) and endothelium-dependent relaxation were investigated in this study.
Thirty-two adult albino male rabbits, in two- and four-week-treatment groups, were divided into three subgroups: control group (saline-injected) (n=4), 3mg/kg/day (low dose) l-DOPA-injected groups (n=6) and 12mg/kg/day (high dose) l-DOPA-injected groups (n=6). After the intraperitoneal injection treatments, the corpus cavernosum tissues were placed in organ bath chambers. The EFS-mediated responses, and the concentration-response curve to carbachol, sodium nitroprusside (SNP), sildenafil were assessed.
The two-week treatment with high-dose l-DOPA decreased the NO-dependent NANC relaxation responses, while there was no change in the low-dose two- and four-week treatment groups. The NO-independent NANC relaxation responses in the two-week groups decreased, and the responses in the four-week groups were unchanged when compared to the controls. The relaxation responses to carbachol showed no differences among all groups except for the high-dose four-week l-DOPA group. The relaxation responses of SNP and sildenafil were increased in all of the treatment groups when compared to the controls.
The observed increases in SNP- and sildenafil-induced responses, along with the decreased EFS-mediated responses, suggest increased sensitivity in the NO-signalling pathway following l-DOPA administration.
多巴胺是一种关键的中枢神经递质，在动物和人类阴茎反射的自主和躯体成分中发挥着重要作用。与多巴胺的勃起反应类似，左旋多巴的全身给药在某些物种中会诱发打哈欠和阴茎勃起。本研究调查了左旋多巴对电场刺激（EFS）介导的一氧化氮（NO）依赖性和非依赖性非肾上腺素能非胆碱能（NANC）舒张反应以及内皮依赖性舒张的可能影响。
将32只成年白化雄性兔子分为两周治疗组和四周治疗组，再分为三个亚组：对照组（注射生理盐水）（n = 4）、3mg/kg/天（低剂量）左旋多巴注射组（n = 6）和12mg/kg/天（高剂量）左旋多巴注射组（n = 6）。腹腔注射治疗后，将海绵体组织置于器官浴槽中。评估EFS介导的反应以及对卡巴胆碱、硝普钠（SNP）、西地那非的浓度-反应曲线。
高剂量左旋多巴两周治疗降低了NO依赖性NANC舒张反应，而低剂量两周和四周治疗组无变化。与对照组相比，两周组的NO非依赖性NANC舒张反应降低，四周组的反应未改变。除高剂量四周左旋多巴组外，所有组对卡巴胆碱的舒张反应均无差异。与对照组相比，所有治疗组中SNP和西地那非的舒张反应均增加。
观察到的SNP和西地那非诱导反应的增加以及EFS介导反应的降低表明，左旋多巴给药后NO信号通路的敏感性增加。
