Valenzuela R, Li C H, Huidobro-Toro J P
Department of Physiology, Neurohumoral Regulatory Unit, Faculty of Biological Sciences, Catholic University of Chile, Casilla, Santiago.
J Pharm Pharmacol. 1989 Feb;41(2):92-6. doi: 10.1111/j.2042-7158.1989.tb06400.x.
The 1-27 truncated fragment of beta h-endorphin (beta h-EP) as well as [Gln8,Gly31]-beta h-EP-Gly-Gly-NH2 or [Arg9,19,24,28,29]-beta h-EP exhibited opiate agonist activity in the rat vas deferens bioassay; the potency of these peptides was 3 to 6 times less than that of beta h-EP. None of these compounds exhibited any degree of antagonism towards the inhibitory action of beta h-EP. Naloxone antagonized and reversed the inhibitory action of beta h-EP and its analogues though with varying potencies. The apparent naloxone-pA2 value for beta h-EP was 8.94; that for [Gln8-Gly31]-beta h-EP-Gly-Gly-NH2 was 8.08 and that for [Arg9,19,24,28,29]-beta h-EP was 8.38. beta-Funaltrexamine (beta-FNA) potently antagonized the inhibitory action of beta h-EP following non-equilibrium kinetics. Tissue preincubation with 10 nM beta-FNA for 60 min followed by extensive washing caused a 10-fold increase in the beta h-EP IC50. However, 10 nM beta-FNA caused only a 1.2 increase in the IC50 of [Gln8,Gly31]-beta h-EP-Gly-Gly-NH2 and a 4.1-fold increase in the IC50 of [Arg9,19,24,28,29]-beta h-EP. In contrast, preincubation of the tissue with 3 microM ICI 174,864 did not modify the potency of beta h-EP or its structural analogues. However, a 60 min pretreatment with 10 microM beta-FNA followed by the addition of 3 microM ICI 174,864 revealed a further decrease in the potency of the opiopeptins compared with tissues exposed to beta-FNA alone or ICI 174,864 alone. In conclusion, the inhibitory action of these peptides is remarkably sensitive to beta-FNA antagonism; in addition the peptides act as pure opiate agonists in marked contrast with the agonist-antagonist properties described in the CNS.
β内啡肽（βh - EP）的1 - 27截短片段以及[Gln8,Gly31]-βh - EP - Gly - Gly - NH2或[Arg9,19,24,28,29]-βh - EP在大鼠输精管生物测定中表现出阿片类激动剂活性；这些肽的效力比βh - EP低3至6倍。这些化合物对βh - EP的抑制作用均未表现出任何程度的拮抗作用。纳洛酮能拮抗并逆转βh - EP及其类似物的抑制作用，但其效力各不相同。βh - EP的表观纳洛酮 - pA2值为8.94；[Gln8 - Gly31]-βh - EP - Gly - Gly - NH2的为8.08，[Arg9,19,24,28,29]-βh - EP的为8.38。β - 芬太尼（β - FNA）按照非平衡动力学有效拮抗βh - EP的抑制作用。用10 nM β - FNA对组织进行60分钟预孵育，然后充分洗涤，导致βh - EP的IC50增加10倍。然而，10 nM β - FNA仅使[Gln8,Gly31]-βh - EP - Gly - Gly - NH2的IC50增加1.2倍，使[Arg9,19,24,28,29]-βh - EP的IC50增加4.1倍。相比之下，用3 μM ICI 174,864对组织进行预孵育并未改变βh - EP或其结构类似物的效力。然而，用10 μM β - FNA进行60分钟预处理，然后加入3 μM ICI 174,864，与单独暴露于β - FNA或ICI 174,864的组织相比，阿片肽的效力进一步降低。总之，这些肽的抑制作用对β - FNA拮抗作用非常敏感；此外，与中枢神经系统中描述的激动剂 - 拮抗剂特性形成显著对比的是，这些肽表现为纯阿片类激动剂。
