Dodson B A, Miller K W
Anesthesiology. 1985 May;62(5):615-20. doi: 10.1097/00000542-198505000-00013.
Loss of righting reflex (LRR) produced by various concentrations of the leucine-enkephalin analog BW831c (TYR.D-ALA.GLY.PHE.D-LEU.NHEt.HCI) was determined in amphibia at 1 atm and 120 atm of helium. EC50 for LRR was 22.1 +/- 1.6 microM and 44 +/- 6.9 microM, respectively. The octanol/water partition coefficient (P) was 26 +/- 3.6, suggesting that this peptide is sufficiently lipid soluble for a classic Meyer-Overton type of anesthetic action. The ratio (EC50 at 120 atm)/(EC50 at 1 atm) for the peptide (2.0 +/- 0.31) was essentially the same as that for the long-chain alcohol, octanol (1.8 +/- 0.08), and similar to those reported for phenobarbital and the gaseous anesthetics. Thus, peptide-induced LRR was reversible by pressure. Peptide-induced LRR also was completely reversible by naloxone, whereas octanol-induced LRR was unaffected by up to 100 microM naloxone. These findings are consistent with a dual mechanism of anesthetic action for this peptide: one, an opiate receptor-specific mechanism, reversible with the specific opiate antagonist, naloxone; the other, a nonspecific mechanism, related to lipid solubility and reversible with the application of the physical agent, pressure.
在两栖动物中，于1个大气压和120个大气压的氦气环境下，测定了不同浓度的亮氨酸脑啡肽类似物BW831c（酪氨酸-D-丙氨酸-甘氨酸-苯丙氨酸-D-亮氨酸-N-乙基盐酸盐）所产生的翻正反射丧失（LRR）情况。LRR的半数有效浓度（EC50）分别为22.1±1.6微摩尔/升和44±6.9微摩尔/升。正辛醇/水分配系数（P）为26±3.6，这表明该肽具有足够的脂溶性，可产生经典的迈耶-奥弗顿类型的麻醉作用。该肽的（120个大气压下的EC50）/（1个大气压下的EC50）比值（2.0±0.31）与长链醇正辛醇的比值（1.8±0.08）基本相同，且与苯巴比妥和气态麻醉剂所报道的比值相似。因此，肽诱导的LRR可被压力逆转。肽诱导的LRR也可被纳洛酮完全逆转，而正辛醇诱导的LRR在高达100微摩尔/升的纳洛酮作用下不受影响。这些发现与该肽的双重麻醉作用机制一致：其一，为阿片受体特异性机制，可被特异性阿片拮抗剂纳洛酮逆转；其二，为非特异性机制，与脂溶性有关，可通过施加物理因素压力而逆转。
