An analogue of thyrotropin-releasing hormone, DN1417, decreases naloxone binding in the rat brain.
We explored whether thyrotropin-releasing hormone may affect opioid receptors in the rat brain. Adult male rats were intraperitoneally injected twice a day with varying doses of DN1417, a potent analogue of thyrotropin-releasing hormone, for 2 days, and opioid receptors of the brain (hypothalamus, striatum, hippocampus, midbrain, ponsmedulla, and cortex) homogenates were determined using [3H]naloxone. Intraperitoneal injection of DN1417 in a dose of 0.3 mg/100 g body wt resulted in a significant reduction in naloxone binding of the striatum as compared with the saline-injected group, whereas naloxone binding of other brain regions was not affected by DN1417. DN1417 produced a dose-dependent decrease in naloxone binding of the striatum. The affinity constant of naloxone binding was similar between the saline- and DN1417-injected groups. In vitro addition of DN1417 did not interfere with the brain naloxone binding. The distribution of 3H-labeled DN1417 injected peritoneally did not differ among the brain regions. The present data imply that the opioid antagonistic action of thyrotropin-releasing hormone may be due, at least in part, to the significant decrease in the striatal opioid binding in the rat brain.
Mori
M
M
First Department of Internal Medicine, Gunma University, School of Medicine, Maebashi, Japan.
Michimata
T
T
Ishihara
H
H
Yamada
M
M
Iriuchijima
T
T
Kobayashi
S
S
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D006728:Hormones; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009270:Naloxone / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects / Q000378:metabolism*; D013973:Thyrotropin-Releasing Hormone / Q000493:pharmacokinetics / Q000494:pharmacology / Q000031:analogs & derivatives; D014018:Tissue Distribution
D006728:Hormones; D011957:Receptors, Opioid; D009270:Naloxone; D013973:Thyrotropin-Releasing Hormone; C029762:DN 1417