4-(2'-Methoxy-phenyl)-1-[2'-(n-2"-pyridinyl)-p-iodobenzamido]-ethyl- piperazine ([125I]p-MPPI) as a new selective radioligand of serotonin-1A sites in rat brain: in vitro binding and autoradiographic studies.
4-(2'-Methoxy-phenyl)-1-[2'-(n-2"-pyridinyl)-p-iodobenzamido]-ethyl- piperazine ([125I]p-MPPI) as a new selective radioligand of serotonin-1A sites in rat brain: in vitro binding and autoradiographic studies.
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发表时间：
1995
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通讯作者：
M. Kung;D. Frederick;M. Mu;Z. Zhuang;H. Kung
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作者：
M. Kung;D. Frederick;M. Mu;Z. Zhuang;H. Kung
用离体匀浆结合和放射自显影技术评价了放射性碘标记5-羟色胺-1A（5-HT_（1A））受体拮抗剂4-（2 ′-甲氧基-苯基）-1-[2 ′-（n-2”-吡啶基）-p-碘苯甲酰氨基]-乙基-哌嗪（[~（125）I]p-MPPI）在大鼠脑中的结合特性。在大鼠海马匀浆中，[125 I]p-MPPI显示Kd值为0.32 +/- 0.04 nM（存在MgCl 2时），Bmax值为315 +/- 60 fmol/mg蛋白质。[125 I]p-MPPI标记的5-HT 1A受体数量比放射性碘标记的5-HT 1A激动剂反式-8-羟基-2-（N-正丙基-N-3 '-碘-2'-丙烯基）氨基四氢萘（[125 I]R（+）8-OH-PIPAT）（225 +/- 47 fmol/mg蛋白质）标记的数量高40%。镁离子对[125 I]p-MPPI结合有抑制作用，但对[125 I]R（+）8-OH-PIPAT的特异性结合有增强作用。在鸟苷酸存在下，观察到[125 I]p-MPPI的Bmax值显著增加（对照，307 +/-35 fmol/mg蛋白质; GTP，345 +/-30 fmol/mg蛋白质;鸟苷酰-亚氨基二磷酸，362 +/-35 fmol/mg蛋白质）;然而，两种鸟苷酸都显著降低了[125 I]R（+）8-OH-PIPAT测定的Bmax值（对照，213 +/-50 fmol/mg蛋白质; GTP，133 +/-20 fmol/mg蛋白质;鸟苷酰-亚氨基二磷酸，108 +/-20 fmol/mg蛋白质）。[125 I]p-MPPI与5-HT 1A受体的结合特性表明p-MPPI是5-HT 1A受体的拮抗剂。用[125 I]p-MPPI对大鼠脑切片进行体外放射自显影研究，结果显示5-HT 1A受体富集区特异性标记，区域分布与[125 I]R（+）8-OH-PIPAT标记的区域密切匹配。（250字处删节）
Binding characteristics of a radioiodinated serotonin-1A (5-HT1A) receptor antagonist, 4-(2'-methoxy-phenyl)-1-[2'-(n-2"-pyridinyl)-p- iodobenzamido]-ethyl-piperazine ([125I]p-MPPI) were evaluated using in vitro homogenate binding and autoradiographic techniques in rat brains. [125I]p-MPPI displayed a Kd value of 0.32 +/- 0.04 nM (in the presence of MgCl2) and a Bmax value of 315 +/- 60 fmol/mg of protein in rat hippocampal homogenates. The number of 5-HT1A receptors labeled by [125I]p-MPPI was 40% higher than that labeled by trans-8-hydroxy-2-(N-n-propyl-N-3'-iodo-2'- propenyl)aminotetralin ([125I]R(+)8-OH-PIPAT) (225 +/- 47 fmol/mg of protein), a radioiodinated 5-HT1A agonist. The magnesium ion showed an inhibitory effect on [125I]p-MPPI binding but increased the specific binding of [125I]R(+)8-OH-PIPAT. A significant increase in Bmax values in the presence of guanyl nucleotides was observed for [125I]p-MPPI (control, 307 +/- 35 fmol/mg of protein; with GTP, 345 +/- 30 fmol/mg of protein; with guanylyl-imidodiphosphate, 362 +/- 35 fmol/mg of protein); however, both guanyl nucleotides significantly reduced the Bmax values measured by [125I]R(+)8-OH-PIPAT (control, 213 +/- 50 fmol/mg of protein; with GTP, 133 +/- 20 fmol/mg of protein; with guanylyl-imidodiphosphate, 108 +/- 20 fmol/mg of protein). The binding characteristics of [125I]p-MPPI for 5-HT1A receptors suggest that p-MPPI is an antagonist for 5-HT1A receptors. In vitro autoradiographic studies in rat brain sections with [125I]p-MPPI showed specific labeling of areas rich in 5-HT1A receptors and the regional distribution closely matched those labeled by [125I]R(+)8-OH-PIPAT.(ABSTRACT TRUNCATED AT 250 WORDS)