Proenkephalin A fragments exhibit spinal and supraspinal opioid activity in vivo.
Proenkephalin A fragments exhibit spinal and supraspinal opioid activity in vivo.
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发表时间：
1985-12
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通讯作者：
A. Dray;L. Nunan;W. Wire
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作者：
A. Dray;L. Nunan;W. Wire
在麻醉大鼠中等距记录的反射性膀胱收缩的抑制被用作中枢阿片活性的指标。膀胱活动的抑制已被证明是介导的脊髓和脊髓上的μ和δ阿片受体。使用该模型，测试脑啡肽原A分子的许多神经肽片段（肽F、肽E、BAM 22 P、BAM 12 P、Met 5-脑啡肽-Arg 6、Phe 7、Leu 8、Met 5-脑啡肽-Arg 6、Phe 7、Met-脑啡肽、Leu-脑啡肽）的体内活性。当通过团注微量注射到侧脑室（i. c. v.）或鞘内注入脊髓蛛网膜下腔（L3和L4椎骨之间）。较大分子量的肽比较小分子量的肽对膀胱活动产生更长时间的抑制，在脊髓和脊髓上部位的活性等级顺序相似：肽F大于或等于肽E = BAM 22 P大于BAM 12 P大于Met 5-脑啡肽-Arg 6，Phe 7，Leu 8 = Met 5-脑啡肽-Arg 6，Phe 7大于或等于Met-脑啡肽= Leu-脑啡肽。使用阿片样物质拮抗剂纳洛酮（μ受体）和ICI 174，864（N，N-二烯丙基-Tyr-Aib-Aib-Phe-Leu-OH：Aib = α-氨基异丁酸）（δ受体）进一步测定每个片段的相对受体选择性。将每种拮抗剂对等有效剂量的高选择性阿片受体配体[D-Ala 2，Me-Phe 4，Gly（ol）5]脑啡肽（μ受体）和[D-Pen 2，D-Pen 5]脑啡肽（δ受体）的活性（Ke）与对脑啡肽原A片段的活性（Ke）进行比较。（250字处删节）
The inhibition of reflex urinary bladder contractions, recorded isometrically in the urethane-anesthesized rat, was used as an index of central opioid activity. Inhibition of bladder activity has been shown to be mediated both spinally and supraspinally by mu and delta opioid receptors. Using this model a number of neuropeptide fragments of the proenkephalin A molecule (peptide F, peptide E, BAM 22P, BAM 12P, Met5-enkephalin-Arg6,Phe7,Leu8, Met5-enkephalin-Arg6,Phe7, Met-enkephalin, Leu-enkephalin) were tested for in vivo activity. Each of the fragments inhibited reflex bladder contractions when administered by bolus microinjection into a lateral ventricle (i.c.v.) or intrathecally into the spinal subarachnoid space (between L3 and L4 vertebra). The larger molecular weight peptides produced more prolonged inhibition of bladder activity than the smaller molecular weight ones, with the rank order of activity being similar at spinal and supraspinal sites: peptide F greater than or equal to peptide E = BAM 22P greater than BAM 12P greater than Met5-enkephalin-Arg6,Phe7,Leu8 = Met5-enkephalin-Arg6,Phe7 greater than or equal to Met-enkephalin = Leu-enkephalin. The relative receptor selectivity of each fragment was further determined using the opioid antagonists naloxone (mu receptors) and ICI 174,864 (N, N-diallyl-Tyr-Aib-Aib-Phe-Leu-OH: Aib = alpha-aminoisobutyric acid) (delta receptors). The activity (Ke) of each antagonist against equieffective doses of the highly selective opioid receptor ligands [D-Ala2,Me-Phe4,Gly(ol)5]enkephalin (mu receptors) and [D-Pen2,D-Pen5]enkephalin (delta receptors) was compared with that against the proenkephalin A fragments.(ABSTRACT TRUNCATED AT 250 WORDS)