Luce Valeria, Fernandez Solari Javier, Rettori Valeria, De Laurentiis Andrea
Centro de Estudios Farmacológicos y Botánicos, CEFYBO-CONICET-UBA, Facultad de Medicina, Paraguay 2155, 1121ABG, Argentina.
Cátedra de Fisiología, Facultad de Odontología, Universidad de Buenos Aires, Marcelo T. de Alvear 2142, 1122 ABG Buenos Aires, Argentina.
Regul Pept. 2014 Jan 10;188:31-9. doi: 10.1016/j.regpep.2013.12.004. Epub 2013 Dec 14.
The neurohypophyseal hormones oxytocin (OT) and vasopressin (VP) are involved in behavioral, autonomic and neuroendocrine functions. Both peptides are synthesized in magnocellular neurons of paraventricular and supraoptic nuclei at hypothalamic level whose axons terminate in the neurohypophysis (NH), from where OT and VP are released into the systemic circulation. NH contains abundant nitric oxide (NO) synthase suggesting that NO plays a role in the release of these neuropeptides. The endocannabinoid system is present in magnocellular neurons of the hypothalamic neurohypophyseal system, and we have previously demonstrated that endocannabinoids modulate OT secretion at hypothalamic level. In the present work, we investigated the in vitro effect of the endocannabinoid anandamide (AEA) on OT and VP release from NH of untreated adult male rats and the involvement of NO in this action. Our results showed that AEA decreased OT and VP secretion from NH. AEA action was mediated by NO, since the inhibition of NO synthesis completely blocked this inhibitory effect. We found that cannabinoid receptor type 2 (CB2) and transient receptor potential cation channel subfamily V member 1 (TRPV1) are involved in the inhibitory effect of AEA because AM630 and capsazepine, CB2 and TRPV1 antagonists respectively, but not AM251, a CB1 antagonist, blocked AEA effect at neurohypophyseal level. These findings revealed an interaction between endocannabinoid, nitric oxide and oxytocin/vasopressin systems that could be involved in the modulation of homeostatic, behavioral and reproductive processes.
神经垂体激素催产素（OT）和血管加压素（VP）参与行为、自主神经和神经内分泌功能。这两种肽均在下丘脑水平的室旁核和视上核的大细胞神经元中合成，其轴突终止于神经垂体（NH），OT和VP从神经垂体释放进入体循环。神经垂体含有丰富的一氧化氮（NO）合酶，提示NO在这些神经肽的释放中起作用。内源性大麻素系统存在于下丘脑神经垂体系统的大细胞神经元中，我们之前已经证明内源性大麻素在下丘脑水平调节OT分泌。在本研究中，我们研究了内源性大麻素花生四烯酸乙醇胺（AEA）对未处理成年雄性大鼠神经垂体释放OT和VP的体外作用以及NO在此作用中的参与情况。我们的结果表明，AEA降低了神经垂体中OT和VP的分泌。AEA的作用是由NO介导的，因为抑制NO合成完全阻断了这种抑制作用。我们发现2型大麻素受体（CB2）和瞬时受体电位阳离子通道亚家族V成员1（TRPV1）参与了AEA的抑制作用，因为分别作为CB2和TRPV1拮抗剂的AM630和辣椒素阻断了AEA在神经垂体水平的作用，但CB1拮抗剂AM251没有此作用。这些发现揭示了内源性大麻素、一氧化氮和催产素/血管加压素系统之间的相互作用，这可能参与了稳态、行为和生殖过程的调节。
