[Des-Tyr1]dynorphin A-(2-17) has naloxone-insensitive antinociceptive effect in the writhing assay.
[Des-Tyr1]dynorphin A-(2-17) has naloxone-insensitive antinociceptive effect in the writhing assay.
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发表时间：
1995-05
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通讯作者：
L. Hooke;L. He;N. Lee
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作者：
L. Hooke;L. He;N. Lee
强啡肽家族的肽在阿片类药物中脱颖而出，因为其成员在常见的抗伤害性测定中在中枢给药后不具有抗伤害性。此外，关于脊髓抗伤害感受的报道一直相互矛盾。我们在扭体试验中测试了静脉注射强啡肽A-（1-13）的抗伤害活性，发现它非常有效，ED 50为1.0（0.99-1.02）mumol/kg。值得注意的是，[des-tyr 1]dyn A-（2-17）具有相同的活性，ED 50为1.1（0.99-1.20）。这种活性也保留了几个较小的，非阿片类强啡肽A片段，不受50 μ mol/kg纳洛酮或20 μ mol/kg Nor-BNI的存在。此外，ED 50值在吗啡依赖小鼠中没有差异。在给药后5 min观察到dyn A-（1-13）和A-（2-17）的峰值效应，静脉给药后1 h仍可测量到dyn A-（1-13）或dyn A-（2-17）的效应，此时ED 50增加5- 6倍。i.c.v.和i.t.强啡肽A-（1-13）给药后的效应与文献报道的相似。强啡肽A（2-17）经上述途径也有效，其ED_（50）值与强啡肽A-（1-13）的ED_（50）值无显著差异。当腹腔注射时，dyn A-（1-13）和A-（2-17）两者也是活性的，而ED 50值在s.c.局（250字处删节）
The dynorphin family of peptides stands out among the opioids in that its members are not antinociceptive after central administration in the common antinociceptive assays. In addition, reports of spinal antinociception have been conflicting. We have tested the antinociceptive activity of i.v. dynorphin A-(1-13) in the writhing assay and have found it to be very potent, with an ED50 of 1.0 (0.99-1.02) mumol/kg. Remarkably, [des-tyr1]dyn A-(2-17) was equally active with an ED50 of 1.1 (0.99-1.20). This activity was also retained by several smaller, non-opioid dynorphin A fragments and was not affected by the presence of either 50 mumol/kg naloxone or 20 mumol/kg Nor-BNI. Further, ED50 values were not different in morphine-dependent mice. The peak effect of dyn A-(1-13) and A-(2-17) was observed 5 min after administration and the effect of dyn A-(1-13) or dyn A-(2-17) was still measurable 1 hr after i.v. administration with a 5- to 6-fold increase in ED50 at this time. The ED50 values after i.c.v. and i.t. administration of dyn A-(1-13) were similar to those reported previously. Dyn A(2-17) was also effective by these routes with ED50 values not significantly different from those of dyn A-(1-13). Both dyn A-(1-13) and A-(2-17) were also active when injected i.p., whereas ED50 values increased substantially after s.c. administration.(ABSTRACT TRUNCATED AT 250 WORDS)