摘要
目的进一步阐明胍丁胺对阿片药理作用的影响。方法采用小鼠醋酸扭体法、小鼠热辐射甩尾法、小鼠热板法评价了精氨酸及精氨酸脱羧酶抗体对痛阈、吗啡镇痛及其耐受作用的影响。结果在小鼠醋酸扭体实验中,脑室注射精氨酸能剂量依赖性地抑制小鼠扭体次数,最大抑制率达84 %。在小鼠热辐射甩尾模型中,精氨酸不影响小鼠的甩尾时间,但能剂量依赖性地增强吗啡的镇痛作用,使吗啡2 .5 mg·kg-1的最大可能镇痛百分率从23 %增加到71 %。此外,在小鼠热辐射甩尾实验中,精氨酸能抑制吗啡100 mg·kg-1所诱导的急性耐受。精氨酸上述作用可被咪唑啉受体拮抗剂咪唑克生(3mg·kg-1,ip)所抑制。在小鼠热辐射甩尾实验和小鼠55℃热板实验中,精氨酸脱羧酶抗体能抑制吗啡镇痛,并能加重吗啡所致的耐受。结论上述结果提示,精氨酸及精氨酸脱羧酶在痛阈、吗啡镇痛及吗啡依赖形成过程中具有重要作用。
AIM To further elucidate the role of agmatine on the pharmacological effects of opioids. METHODS The effect of L-arginine and L-arginine decarboxylase（L-ADC） antibodies on pain threshold, morphine antinociception and tolerance were investigated in mouse acetic acid writhing test, mouse radiant heat tail flick test and mouse hot plate test. RESULTS In mouse acetic acid writhing test, intracerebroventricular injection of L- arginine dose-dependently inhibited the writhing of mice compared with saline control. L-arginine did not influence tile tail flick latency itself in mouse radiant heat tail flick test, but enhanced antinociceptive effect of morphine in a dose-dependent manner. The possible maximal analgesia percentage of morphine 2.5 mg·kg^-1 was increased from 23% to 71%. Furthermore, L-arginine inhibited acute tolerance induced by morphine 100 mg·kg^-1 in mouse radiant heat tail flick test. The effect of L-arginine as mentioned above could be antagonized by idazoxan （3 mg·kg^-1, ip）, which is a selective antagonist of imidazoline receptors. L-ADC specific antibodies inhibited morphine antinociception and promoted the development of tolerance to morphine in mouse radiant heat tail flick test and 55℃ hot plate test. CONCLUSION L-Arginine and L-ADC play important roles in the formation of pain threshold, morphine antinociception and tolerance.
出处
《中国药理学与毒理学杂志》
CAS
CSCD
北大核心
2005年第4期241-247,共7页
Chinese Journal of Pharmacology and Toxicology
基金
国家重点基础研究发展计划(2003CB515400)
国家高科技研究发展计划(2002AA2Z3128)~~
关键词
精氨酸
精氨酸脱羧酶
胍丁胺
镇痛
吗啡耐受
L-arginine
L-arginine decarboxylase
agmatine
analgesia
morphine tolerance
