Garaulet J V, Laorden M L, Milanés M V
Department of Physiology and Pharmacology, University School of Medicine, Murcia, Spain.
Eur J Pharmacol. 1992 Nov 13;223(1):19-23. doi: 10.1016/0014-2999(92)90813-j.
Electrically stimulated guinea-pig ileum myenteric plexus-longitudinal muscle was used to determine if changes in temperature alter the inhibitory effects of DAGO ([D-Ala2,N-MePhe4,Gly5-ol]enkephalin, mu-agonist), DPDPE ([D-Pen2,-Pen5] enkephalin, delta-agonist) and U-50,488H (trans-3,4-dichloro)-N-methyl-N-[2-(1- pyrrolidynyl)cyclohexyl]benzeneacetamide methane sulfonate, kappa-agonist). The potency (expressed as the concentration which produces 50% inhibition, IC50) of DAGO and DPDPE was significantly (P < 0.05) decreased at 30 degrees C (8.8 +/- 2.7 x 10(-9) and 8325.2 +/- 1070 x 10(-9) M), when compared to the potency at 37 degrees C (3.8 +/- 0.3 x 10(-9) and 6298.6 +/- 320 x 10(-9) M). Higher temperature (40 degrees C) did not modify the potency of DAGO or DPDPE compared to that at 37 degrees C. However, the potency of U-50,488H was significantly (P < 0.01) increased at 40 degrees C (0.7 +/- 0.0 x 10(-9) M) versus 37 degrees C (2.4 +/- 0.9 x 10(-9) M) or 30 degrees C (2.5 +/- 0.3 x 10(-9) M). The kappa-agonist was more potent than DAGO or DPDPE at 30 or 40 degrees C. These data demonstrate that changes in temperature can alter the potency of opioid agonists.
用电刺激豚鼠回肠肌间神经丛 - 纵行肌来确定温度变化是否会改变DAGO（[D - Ala2，N - MePhe4，Gly5 - ol]脑啡肽，μ - 激动剂）、DPDPE（[D - Pen2，-Pen5]脑啡肽，δ - 激动剂）和U - 50,488H（反式 - 3,4 - 二氯）-N - 甲基 - N - [2 - (1 - 吡咯烷基)环己基]苯乙酰胺甲磺酸盐，κ - 激动剂）的抑制作用。与37℃时的效力（3.8±0.3×10⁻⁹和6298.6±320×10⁻⁹ M）相比，DAGO和DPDPE在30℃时的效力（分别为8.8±2.7×10⁻⁹和8325.2±1070×10⁻⁹ M）显著降低（P < 0.05）。与37℃时相比，更高温度（40℃）并未改变DAGO或DPDPE的效力。然而，与37℃（2.4±0.9×10⁻⁹ M）或30℃（2.5±0.3×10⁻⁹ M）相比，U - 50,488H在40℃时的效力显著增加（P < 0.01）（0.7±0.0×10⁻⁹ M）。在30℃或40℃时，κ - 激动剂比DAGO或DPDPE更有效。这些数据表明温度变化可改变阿片类激动剂的效力。
