De Laurentiis A, Pisera D, Duvilanski B, Rettori V, Lasaga M, Seilicovich A
Centro de Investigaciones en Reproducción, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina.
Brain Res Bull. 2000 Oct;53(3):325-30. doi: 10.1016/s0361-9230(00)00356-7.
Neurokinin A (NKA) is a tachykinin that participates in the control of neuroendocrine functions. The posterior pituitary lobe (PP) contains abundant nitric oxide synthase (NOS), suggesting that nitric oxide (NO) may play a role in controlling the release of neuropeptides and neurotransmitters. In the present project, we investigated the in vitro effect of NKA on oxytocin release from hypothalamic explants and PP of male rats and the possible involvement of NO in the action of NKA. Since NKA inhibits gamma-aminobutyric acid (GABA) release from PP, we also examined the role of NO in the effect of NKA on basal and K(+)-evoked GABA release. NKA (10(-7)-10(-5) M) significantly decreased oxytocin release from PP, whereas it did not affect its release from hypothalamic explants. The inhibitory effect of NKA on oxytocin release from PP was completely blocked by the NOS inhibitors N(G)-monomethyl-L-arginine (L-NMMA, 0.5 mM) or N(G)-nitro-L-arginine-methyl-ester (L-NAME, 1 mM). Sodium nitroprusside (0.5 mM), an NO releaser, had no effect on basal GABA release but significantly decreased K(+)-evoked GABA release. L-NMMA (0.3 mM) and L-NAME (0.5 mM) increased K(+)-evoked GABA release, indicating that NO plays an inhibitory role in GABA release from PP. The inhibition in both basal and K(+)-evoked GABA release induced by NKA (10(-7) M) was reduced by L-NAME (1 mM). Also, NKA (10(-7) M) increased NO synthesis as measured by [(14)C] citrulline production. Considered all together, our data indicate that NO may mediate the inhibitory effect of NKA on the release of both oxytocin and GABA from PP.
神经激肽A（NKA）是一种速激肽，参与神经内分泌功能的调控。垂体后叶（PP）含有丰富的一氧化氮合酶（NOS），这表明一氧化氮（NO）可能在控制神经肽和神经递质的释放中发挥作用。在本研究中，我们研究了NKA对雄性大鼠下丘脑外植体和垂体后叶催产素释放的体外作用，以及NO在NKA作用中的可能参与情况。由于NKA抑制垂体后叶γ-氨基丁酸（GABA）的释放，我们还研究了NO在NKA对基础和钾离子诱发的GABA释放作用中的作用。NKA（10⁻⁷ - 10⁻⁵ M）显著降低垂体后叶催产素的释放，而对下丘脑外植体催产素的释放没有影响。NKA对垂体后叶催产素释放的抑制作用被NOS抑制剂N⁰-单甲基-L-精氨酸（L-NMMA，0.5 mM）或N⁰-硝基-L-精氨酸甲酯（L-NAME，1 mM）完全阻断。一氧化氮供体硝普钠（0.5 mM）对基础GABA释放没有影响，但显著降低钾离子诱发的GABA释放。L-NMMA（0.3 mM）和L-NAME（0.5 mM）增加钾离子诱发的GABA释放，表明NO在垂体后叶GABA释放中起抑制作用。L-NAME（1 mM）可减轻NKA（10⁻⁷ M）对基础和钾离子诱发的GABA释放的抑制作用。此外，如通过[¹⁴C]瓜氨酸生成所测定，NKA（10⁻⁷ M）增加NO的合成。综合所有数据，我们表明NO可能介导NKA对垂体后叶催产素和GABA释放的抑制作用。
