Succu Salvatora, Mascia Maria Stefania, Melis Tiziana, Sanna Fabrizio, Melis Maria Rosaria, Possenti Roberta, Argiolas Antonio
Bernard B. Brodie Department of Neuroscience and Center of Excellence for the Neurobiology of Addiction, University of Cagliari, S.P. Monserrato-Sestu, Km 0.700, 09042 Monserrato (CA), Italy.
Neuropharmacology. 2005 Dec;49(7):1017-25. doi: 10.1016/j.neuropharm.2005.05.015. Epub 2005 Aug 8.
The effect of four peptides derived from the C-terminal portion of rat pro-VGF(556-617) (VGF(556-576), VGF(588-617), VGF(599-617), and VGF(588-597)), on penile erection and nitric oxide production in the paraventricular nucleus of the hypothalamus was studied in male rats after injecting into this hypothalamic nucleus. VGF(588-617) (0.5, 1 and 2 microg), VGF(599-617) (0.5, 2 and 5 microg) and, to a lower extent, VGF(588-597) (2 and 5 microg) induced penile erection episodes when injected into the paraventricular nucleus and concomitantly increased paraventricular nitric oxide production, while VGF(556-576) (5 microg) was ineffective. VGF(588-617)-induced nitric oxide production was reduced by N(G)-nitro-l-arginine methylester (l-NAME) (20 microg), a nitric oxide synthase inhibitor, which also reduced penile erection when injected in the paraventricular nucleus 15 min before the VGF peptide. The oxytocin receptor antagonist d(CH(2))(5)Tyr(Me)-Orn(8)-vasotocin (1 microg) also effectively reduced VGF(588-617)-induced penile erection when given into the lateral ventricles, but not when injected into the paraventricular nucleus. In both experimental conditions, d(CH(2))(5)Tyr(Me)-Orn(8)-vasotocin was unable to influence nitric oxide production in the paraventricular nucleus. The present results confirm that C-terminal pro-VGF-derived peptides induce penile erection when injected into the paraventricular nucleus and show that this effect is mediated by an increased nitric oxide production in this hypothalamic nucleus. Apparently, this causes the activation of paraventricular oxytocinergic neurons projecting to extra-hypothalamic brain areas and mediating penile erection, as found with dopamine agonists, oxytocin, excitatory amino acids and hexarelin analogue peptides.
研究了源自大鼠前VGF（556 - 617）C末端部分的四种肽（VGF（556 - 576）、VGF（588 - 617）、VGF（599 - 617）和VGF（588 - 597））对雄性大鼠下丘脑室旁核阴茎勃起和一氧化氮产生的影响。将这些肽注射到该下丘脑核后进行研究。VGF（588 - 617）（0.5、1和2微克）、VGF（599 - 617）（0.5、2和5微克）以及在较低程度上VGF（588 - 597）（2和5微克）注射到室旁核时可诱导阴茎勃起发作，并同时增加室旁核一氧化氮的产生，而VGF（556 - 576）（5微克）则无效。VGF（588 - 617）诱导的一氧化氮产生可被一氧化氮合酶抑制剂N（G）-硝基-L-精氨酸甲酯（L-NAME）（20微克）降低，在VGF肽注射前15分钟将L-NAME注射到室旁核时，也可降低阴茎勃起。催产素受体拮抗剂d（CH（2））（5）Tyr（Me）-Orn（8）-血管加压素（1微克）注入侧脑室时也可有效降低VGF（588 - 617）诱导的阴茎勃起，但注入室旁核时则无效。在两种实验条件下，d（CH（2））（5）Tyr（Me）-Orn（8）-血管加压素均无法影响室旁核一氧化氮的产生。目前的结果证实，源自前VGF C末端的肽注射到室旁核时可诱导阴茎勃起，并表明这种作用是由该下丘脑核中一氧化氮产生增加介导的。显然，这会导致投射到下丘脑外脑区并介导阴茎勃起的室旁催产素能神经元的激活，正如多巴胺激动剂、催产素、兴奋性氨基酸和六元瑞林类似肽所发现的那样。
