McCann S M, Rettori V
Adv Biochem Psychopharmacol. 1986;42:173-89.
Intraventricular injection (3V) of GABA can lead to a dose-related increase in plasma LH in ovariectomized (OVX) and OVX, estrogen-primed animals. Since the effects were blocked by the GABA receptor antagonist, bicucculine (B), they appear to be specific. These alterations in plasma LH were accompanied by alterations in hypothalamic LHRH, dopamine (DA) and norepinephrine (NE) content which suggests roles for all three compounds in the genesis of the increase in plasma LH. Since the DA receptor blocker pimozide (P) failed to block the elevation in LH induced by GABA it appears that the effect of GABA on LH release is mediated by NE. Others have found that the GABA agonist, muscimol, can lower plasma LH under certain conditions. Consequently, it appears likely that there may be opposite actions of GABA on LHRH release depending on the site of action within the hypothalamus. Intravenous (iv) injection of B in OVX rats produced an initial fall in plasma LH followed by a prolonged rise which again suggests several sites of action of GABA on LH release. GABA had no effect on FSH release consistent with separate control of this hormone. 3V injection of various doses of GABA produced a dose-related lowering of plasma TSH in OVX rats which appeared to be mediated by the dopaminergic system since P abolished the TSH-lowering of GABA. Following iv injection of B in normal male rats, there was a dramatic decline in TSH suggesting that under these conditions GABA would have a stimulatory action. Similar results were seen in OVX rats. The results indicate an important stimulatory action of GABA on TSH release in both males and OVX females. Perhaps the discrepancy between the results with B and GABA can be explained again by multiple sites of action of GABA of opposite sign. 3V injection of GABA induced a dose-related stimulation of growth hormone (GH) secretion; however, more recent evidence from other laboratories suggests that under certain conditions GABA has an inhibitory role in GH secretion. Again, we speculate that GABA had dual sites of action of opposite sign to affect GH. In contrast to the effects of GABA on these pituitary hormones, it appears to have a direct inhibitory effect on prolactin (Prl) secretion via the lactotrophs. Both stimulatory and inhibitory actions of GABA have been found following its injection into the brain. Studies with iv B also support dual actions on Prl release.
对去卵巢(OVX)以及去卵巢并用雌激素预处理的动物进行脑室内注射(3V)γ-氨基丁酸(GABA),可导致血浆促黄体生成素(LH)呈剂量相关的增加。由于这些效应被GABA受体拮抗剂荷包牡丹碱(B)所阻断,所以它们似乎具有特异性。血浆LH的这些变化伴随着下丘脑促性腺激素释放激素(LHRH)、多巴胺(DA)和去甲肾上腺素(NE)含量的变化,这表明这三种化合物在血浆LH升高的发生过程中均发挥作用。由于DA受体阻滞剂匹莫齐特(P)未能阻断GABA诱导的LH升高,所以GABA对LH释放的作用似乎是由NE介导的。其他人发现,GABA激动剂蝇蕈醇在某些条件下可降低血浆LH。因此,根据在下丘脑内的作用位点不同,GABA对LHRH释放可能存在相反的作用。对OVX大鼠静脉注射(iv)B,可使血浆LH先下降,随后持续升高,这再次表明GABA对LH释放有多个作用位点。GABA对促卵泡生成素(FSH)释放无影响,这与该激素受独立调控一致。对OVX大鼠进行3V注射不同剂量的GABA,可使血浆促甲状腺激素(TSH)呈剂量相关的降低,这似乎是由多巴胺能系统介导的,因为P可消除GABA对TSH的降低作用。对正常雄性大鼠静脉注射B后,TSH显著下降,这表明在这些条件下GABA具有刺激作用。在OVX大鼠中也观察到了类似结果。这些结果表明,GABA对雄性和OVX雌性动物的TSH释放均具有重要的刺激作用。或许B和GABA结果之间的差异可再次用GABA具有相反作用的多个作用位点来解释。3V注射GABA可诱导生长激素(GH)分泌呈剂量相关的刺激作用;然而,其他实验室最近的证据表明,在某些条件下GABA对GH分泌具有抑制作用。同样,我们推测GABA具有相反作用的双重作用位点来影响GH。与GABA对这些垂体激素的作用不同,它似乎通过促乳素细胞对催乳素(Prl)分泌具有直接抑制作用。将GABA注入脑内后,已发现其具有刺激和抑制作用。静脉注射B的研究也支持其对Prl释放具有双重作用。