GLYCOPEPTIDE ENKEPHALIN ANALOGS PRODUCE ANALGESIA IN MICE - EVIDENCE FOR PENETRATION OF THE BLOOD-BRAIN-BARRIER

被引：219

作者：

POLT, R ^{[1
]}

PORRECA, F ^{[1
]}

SZABO, LZ ^{[1
]}

BILSKY, EJ ^{[1
]}

DAVIS, P ^{[1
]}

ABBRUSCATO, TJ ^{[1
]}

DAVIS, TP ^{[1
]}

HORVATH, R ^{[1
]}

YAMAMURA, HI ^{[1
]}

HRUBY, VJ ^{[1
]}

机构：

[1] UNIV ARIZONA, DEPT PHARMACOL, TUCSON, AZ 85721 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 1994年 / 91卷 / 15期

关键词：

DRUG DELIVERY; OPIOID RECEPTOR; PEPTIDES; ANTINOCICEPTION; GLUCOSIDES;

D O I：

10.1073/pnas.91.15.7114

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Most peptides have not proved useful as neuroactive drugs because they are blocked by the blood-brain barrier and do not reach their receptors within the brain. Intraperitoneally administered L-serinyl beta-D-glucoside analogues of [Met(5)]enkephalin (glycopeptides) have been shown to be transported across the blood-brain barrier to bind with targeted mu- and delta-opioid receptors in the mouse brain. The opioid nature of the binding has been demonstrated with intracerebroventricularly administered naloxone. Paradoxically, glucosylation decreases the lipophilicity of the peptides while promoting transport across the lipophilic endothelial layer. It is suggested that glucose transporter GLUT-1 is responsible for the transport of the peptide message. Profound and long-lasting analgesia has been observed in mice (tail-flick and hot-plate assays) with two of the glycopeptide analogues when administered intraperitoneally.

引用

页码：7114 / 7118

页数：5

共 42 条

[1] POTOCYTOSIS - SEQUESTRATION AND TRANSPORT OF SMALL MOLECULES BY CAVEOLAE [J].