MU-RECEPTOR AND DELTA-RECEPTOR BELONG TO A FAMILY OF RECEPTORS THAT ARE COUPLED TO POTASSIUM CHANNELS
MU-RECEPTOR AND DELTA-RECEPTOR BELONG TO A FAMILY OF RECEPTORS THAT ARE COUPLED TO POTASSIUM CHANNELS
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DOI：
10.1073/pnas.84.15.5487
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发表时间：
1987-08-01
影响因子：
11.1
通讯作者：
CHRISTIE, MJ
中科院分区：
文献类型：
--
作者：
NORTH, RA;WILLIAMS, JT;CHRISTIE, MJ
受体激动剂的作用。和.delta。采用电压箝位法对大鼠蓝斑核神经元和豚鼠粘膜下丛神经元的膜电流进行了比较。在每个组织中，适当的选择性激动剂（tyr - d - ala - gly - mephel - gly -ol）用于。受体在蓝斑或tyrr - d - pen - gly - ph - d - pen。粘膜下神经丛中的受体增加了向内整流钾的电导，并使细胞膜发生了强烈的超极化。两种阿片类药物对钾电导特性的影响无法区分。鸟苷5”-[. γ]细胞内应用的实验。-thio]triphosphate表明鸟嘌呤核苷酸结合调节蛋白参与了阿片受体与钾通道的偶联，但没有证据表明camp依赖性蛋白激酶或蛋白激酶c被激活。值得注意的是，许多脊椎动物神经递质受体与钾通道偶联。与这些通道相关的钾电导具有与.mu激活的电导相似的特性。和.delta。阿片类药物;这个家族包括以下受体：乙酰胆碱M2，去甲肾上腺素。2、多巴胺D2, 5-羟色胺5-HT1，腺苷A1， γ。-氨基丁酸GABAB和生长抑素。这表明，这种电导是一个保守的神经元效应偶联的受体类型之一，介导了几个主要的递质的作用。.mu。和.delta。阿片受体似乎是不寻常的，因为它们都利用相同的效应机制。
The effects of agonists at .mu. and .delta. opioid receptors were compared by measuring membrane currents under voltage clamp from neurons of the rat nucleus locus coeruleus and guinea pig submucous plexus. In each tissue, the appropriate selective agonist (Tyr-D-Ala-Gly-MePhe-Gly-ol for .mu. receptors in locus coeruleus or Tyr-D-Pen-Gly-Phe-D-Pen for .delta. receptors in submucous plexus) increased the conductance of an inwardly rectifying potassium conductance and strongly hyperpolarized the membrane. The properties of the potassium conductance affected by the two opioids could not be distinguished. Experiments with intracellular application of guanosine 5''-[.gamma.-thio]triphosphate indicated that a guanine nucleotide-binding regulatory protein was involved in the coupling between opioid receptor and potassium channel, but there was no evidence for activation of either cAMP-dependent protein kinase or protein kinase C. It is noted that a number of vertebrate neurotransmitter receptors are coupled to potassium channels. The potassium conductance associated with these channels has properties similar to the conductance activated by .mu. and .delta. opioids; this family includes the following receptors: acetylcholine M2, norepinephrine .alpha.2, dopamine D2, 5-hydroxytryptamine 5-HT1, adenosine A1, .gamma.-aminobutyric acid GABAB, and somatostatin. It is suggested that this conductance is a conserved neuronal effector coupled to one of the receptor types that mediates the effects of each of several major transmitters. The .mu. and .delta. opioid receptors appear to be unusual in that both utilize this same effector mechanism.