Coban Taha Abdulkadir, Beydemir Sükrü, Gülçin Ilhami, Ekinci Deniz
Erzincan University, Erzincan Education Faculty, Department of Chemistry Education, 24030 Erzincan, Turkey.
Biol Pharm Bull. 2007 Dec;30(12):2257-61. doi: 10.1248/bpb.30.2257.
Morphine is implicated in diverse functions, from development to immune modulation in the central and peripheral nervous systems. At the present time, morphine is one of the most effective antinociceptive agents used to manage pain. It has been used extensively in the clinical management of pain due to its potent analgesic effect. In this study, the in vitro and in vivo inhibitory effects of morphine on erythrocyte carbonic anhydrase (CA) were investigated. Human erythrocyte isoenzymes, HCA-I and HCA-II, were purified by Sepharose-4B affinity chromatography column with a yield of 66.95 and 62.82%, a specific activity of 3892.3 and 11663.2 EU/mg proteins with 745.1 and 2232.6-fold purification of each isoenzyme, respectively. To determine enzyme purity, sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) was performed. In vitro inhibition of erythrocyte HCA-I and HCA-II by morphine using the CO(2)-hydratase enzyme gave IC(50) values 4.50 x 10(-5) M (r(2): 0.954) and 9.23 x 10(-5) M (r(2): 0.996), respectively. CA activity was significantly attenuated in vivo in Spraque-Dawley rats for up to 3 h (p<0.001) following intraperitoneal administration of morphine. In conclusion, morphine inhibited CA activity both in vitro and in vivo.
吗啡具有多种功能,从发育到中枢和外周神经系统的免疫调节。目前,吗啡是用于控制疼痛的最有效的抗伤害感受药物之一。由于其强大的镇痛作用,它已被广泛用于疼痛的临床管理。在本研究中,研究了吗啡对红细胞碳酸酐酶(CA)的体外和体内抑制作用。通过Sepharose-4B亲和色谱柱纯化人红细胞同工酶HCA-I和HCA-II,产率分别为66.95%和62.82%,比活性分别为3892.3和11663.2 EU/mg蛋白,每种同工酶的纯化倍数分别为745.1和2232.6倍。为了确定酶的纯度,进行了十二烷基硫酸钠-聚丙烯酰胺凝胶电泳(SDS-PAGE)。使用CO(2)-水合酶,吗啡对红细胞HCA-I和HCA-II的体外抑制作用的IC(50)值分别为4.50×10(-5) M(r(2): 0.954)和9.23×10(-5) M(r(2): 0.996)。在Spraque-Dawley大鼠体内,腹腔注射吗啡后长达3小时,CA活性显著降低(p<0.001)。总之,吗啡在体外和体内均抑制CA活性。