Department of Pharmacology & Toxicology, Faculty of Pharmacy, Alexandria University, Egypt.
Pharmacol Res. 2012 Mar;65(3):303-11. doi: 10.1016/j.phrs.2011.12.002. Epub 2011 Dec 13.
The functional role of cholinergic transmission in erection is still far from being fully elucidated. This work aims to further elucidate the modulatory role of neostigmine on NO in the corpus cavernosum and to highlight whether cholinergic transmission in the penis modulates sildenafil action. The isolated rabbit corpus cavernosum and measurement of intracavernosal pressure in the anesthetized rat model were used. Neostigmine (0.02 mg/kg) reduced increase of intracavernosal pressure/mean arterial pressure (ICP/MAP) next to cavernous nerve stimulation. Higher doses (0.06 and 0.4 mg/kg) potentiated ICP/MAP rise and atropine (1.5 and 10 mg/kg) did the opposite. In vitro, neostigmine (10⁻⁵ and 10⁻⁴ M) potentiated neurogenic relaxations and this effect was significantly inhibited by hexamethonium (10⁻⁴ M) or N(ω)-propyl-L-arginine (3 × 10⁻⁵ M) and partially but significantly reduced in the presence of atropine. Lower dose neostigmine (10⁻⁷ M), inhibited electrically induced relaxation over the range of 1-4 Hz, atropine (10⁻⁶ M) almost abolished this inhibitory effect as well as N(G)-nitro-L-arginine (10⁻⁵ M). It was also significantly reduced by selective nNOS inhibitor N(ω)-propyl-L-arginine (3 × 10⁻⁵ M). Nicotine (10⁻⁴ M) significantly potentiated electrically induced relaxations amounting to 84.625 ± 8.06% at 1 Hz and potentiated the effect of sildenafil synergistically. Hexamthonium did the opposite. The potentiatory effect of sildenafil on neurogenic erection was significantly reduced by low dose neostigmine both in vitro and in vivo. This study provides evidence that muscarinic receptors may modulate NO synthesis in nitrergic nerves by inhibiting nNOS and high level of cholinergic stimulation may activate nicotinic receptors to promote erection probably by potentiating NO synthesis in nitrergic nerves.
胆碱能传递在勃起中的功能作用仍远未被充分阐明。本研究旨在进一步阐明新斯的明对阴茎海绵体中一氧化氮（NO）的调节作用，并强调阴茎中的胆碱能传递是否调节西地那非的作用。本研究使用了麻醉大鼠模型中的离体兔阴茎海绵体和测量阴茎海绵体内压。新斯的明（0.02mg/kg）降低了海绵体神经刺激时的阴茎海绵体内压/平均动脉压（ICP/MAP）的增加。更高剂量（0.06 和 0.4mg/kg）增强了 ICP/MAP 的上升，而阿托品（1.5 和 10mg/kg）则相反。在体外，新斯的明（10⁻⁵和 10⁻⁴M）增强了神经源性松弛，这种作用被六烃季铵（10⁻⁴M）或 N（ω）-丙基-L-精氨酸（3×10⁻⁵M）显著抑制，并且在存在阿托品时被部分但显著降低。较低剂量的新斯的明（10⁻⁷M）抑制了 1-4Hz 范围内的电诱导松弛，阿托品（10⁻⁶M）几乎消除了这种抑制作用以及 N（G）-硝基-L-精氨酸（10⁻⁵M）。它也被选择性 nNOS 抑制剂 N（ω）-丙基-L-精氨酸（3×10⁻⁵M）显著降低。尼古丁（10⁻⁴M）显著增强了电诱导松弛，在 1Hz 时达到 84.625±8.06%，并协同增强了西地那非的作用。六烃季铵则相反。在体外和体内，低剂量新斯的明均显著降低了西地那非对神经源性勃起的增强作用。本研究提供的证据表明，毒蕈碱受体可能通过抑制 nNOS 来调节氮能神经中的 NO 合成，而高水平的胆碱能刺激可能通过增强氮能神经中的 NO 合成来激活烟碱受体，从而促进勃起。
