首页> 美国卫生研究院文献>British Journal of Pharmacology and Chemotherapy >Alkylation with beta-funaltrexamine suggests differences between mu-opioid receptor systems in guinea-pig brain and myenteric-plexus.
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Alkylation with beta-funaltrexamine suggests differences between mu-opioid receptor systems in guinea-pig brain and myenteric-plexus.

机译:用β-富纳曲胺烷基化表明豚鼠脑和肌丛神经之间的μ阿片受体系统之间存在差异。

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摘要

1. The effects of pre-incubation with beta-funaltrexamine (beta-FNA) on the binding of [3H]-[D-Ala2, MePhe4, Gly-ol5]enkephalin ([3H]-DAMGO) to homogenates of guinea-pig brain and myenteric-plexus longitudinal muscle have been studied. 2. beta-FNA pretreatment of brain homogenates in Tris-HCl buffer reduced the amount of [3H]-DAMGO binding. This was principally due to a reduction in the maximal number of binding sites measurable. However, approximately 30% of sites labelled by 1 nM [3H]-DAMGO were insensitive to 1 microM beta-FNA. Similar findings were obtained when the alkylation was performed in brain homogenates prepared in Krebs solution buffered with HEPES. 3. beta-FNA pretreatment of whole myenteric-plexus longitudinal muscle strips caused an increase in the IC50 values of mu-agonists, but not of kappa-agonists. However, the binding of [3H]-DAMGO to homogenates of myenteric-plexus longitudinal muscle was not altered by pre-incubation with beta-FNA in Tris-HCl buffer. On the other hand when the pretreatment was carried out in whole tissue in Krebs solution, or in homogenates in the presence of NaCl and Gpp(NH)p, a marked reduction in [3H]-DAMGO binding was observed. 4. These results suggest that a low affinity form of the mu-opioid receptor is the physiologically relevant site for beta-FNA alkylation in the myenteric-plexus and that differences exist between mu-receptor systems in guinea-pig myenteric plexus and brain.
机译:1.预孵育β-富氨曲胺(β-FNA)对[3H]-[D-Ala2,MePhe4,Gly-ol5]脑啡肽([3H] -DAMGO)与豚鼠匀浆结合的影响已经研究了大脑和肌丛神经纵向肌肉。 2.在Tris-HCl缓冲液中对脑匀浆进行β-FNA预处理可减少[3H] -DAMGO结合的量。这主要是由于可测量的结合位点的最大数目减少。但是,大约30%的被1 nM [3H] -DAMGO标记的位点对1 microM beta-FNA不敏感。当在用HEPES缓冲的Krebs溶液中制备的脑匀浆中进行烷基化时,获得了相似的发现。 3.β-FNA预处理整个肌间神经丛纵向肌肉条带导致mu激动剂的IC50值增加,但kappa激动剂的IC50值却没有增加。但是,[3H] -DAMGO与肌间神经丛纵向肌肉匀浆的结合不会通过在Tris-HCl缓冲液中与β-FNA进行预孵育而改变。另一方面,当预处理在Krebs溶液的整个组织中或在NaCl和Gpp(NH)p存在的匀浆中进行时,观察到[3H] -DAMGO结合的明显减少。 4.这些结果表明,μ阿片受体的低亲和力形式是肌间神经丛中β-FNA烷基化的生理相关位点,并且豚鼠肌间神经丛和大脑中的mu受体系统之间存在差异。

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