THE EFFECTS OF PERTUSSIS TOXIN ON DOPAMINE-D2 AND SEROTONIN 5-HT1A AUTORECEPTOR-MEDIATED INHIBITION OF NEUROTRANSMITTER SYNTHESIS - RELATIONSHIP TO RECEPTOR RESERVE
THE EFFECTS OF PERTUSSIS TOXIN ON DOPAMINE-D2 AND SEROTONIN 5-HT1A AUTORECEPTOR-MEDIATED INHIBITION OF NEUROTRANSMITTER SYNTHESIS - RELATIONSHIP TO RECEPTOR RESERVE
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DOI：
10.1016/0028-3908(92)90083-2
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发表时间：
1992-05-01
影响因子：
4.7
通讯作者：
MELLER, E
中科院分区：
文献类型：
--
作者：
BOHMAKER, K;BORDI, F;MELLER, E
纹状体D2多巴胺（DA）自身受体被n-乙氧羰基-2-乙氧基- 1,2 -二氢喹啉（EEDQ）不可逆失活，纹状体鸟嘌呤核苷酸结合蛋白（G蛋白）被百日咳毒素（PT）失活，使n- n-丙基去甲吗啡（NPA）介导的γ -丁内酯（GBL）诱导的l- 3,4-二羟基苯丙氨酸（L-DOPA）升高的抑制作用的剂量-反应曲线向右平移，最大反应降低。相比之下，对于部分激动剂(+)-3-(3-羟基苯基-n- n-丙基哌啶[(+)-3- ppp]， D2受体或G蛋白失活后，ED50几乎没有变化。在中缝核的体树突5-HT1A自身受体中发现了完全类似的作用，介导5-羟色胺（5-HT）合成的抑制；通过测定l -5-羟色氨酸（5-HTP）水平的变化，利用完全激动剂8-羟基-2-（二正丙基氨基）四氢萘林（8-OH-DPAT）和部分激动剂丁螺环酮抑制5-HT的合成。此外，在这两个系统中，与单独使用任何一种药物相比，联合使用百日咳毒素，然后使用EEDQ，降低了最大效果，但对ED50的进一步影响很小。在对激动剂表现出大量受体储备的系统中，如上述系统，受体或G蛋白失活后出现的相同反应模式可能反映了受体储备现象背后的共同机制的运作。
Irreversible inactivation of striatal D2 dopamine (DA) autoreceptors with N-ethoxycarbonyl-2-ethoxy-1, 2-dihydroquinoline (EEDQ) or inactivation of striatal guanine nucleotide binding proteins (G proteins) with pertussis toxin (PT) shifted the dose-response curve for N-n-propylnorapomorphine (NPA)-mediated inhibition of gamma-butyrolactone (GBL)-induced elevation Of L-3,4-dihydroxyphenylalanine (L-DOPA) to the right, with a decrease in the maximum response. For the partial agonist (+)-3-(3-hydroxyphenyl-N-n-propylpiperidine [(+)-3-PPP], in contrast, there was little shift in the ED50, after inactivation of either D2 receptors or G proteins. Completely analogous effects were found at the somatodendritic 5-HT1A autoreceptor in the raphe nuclei, mediating inhibition of the synthesis of serotonin (5-HT); the full agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and the partial agonist, buspirone were utilized to inhibit the synthesis of 5-HT, as measured by changes in levels of L-5-hydroxytryptophan (5-HTP). Additionally, in both systems, combined treatment with pertussis toxin, followed by EEDQ, reduced the maximum effect, when compared to either agent alone but had little further effect on the ED50. In systems exhibiting a large receptor reserve for agonists, such as those described above, the same pattern of response seen after inactivation of receptors or G proteins may reflect the operation of a common mechanism underlying the phenomenon of receptor reserve.