Abstract
The effect of morphine and other narcotic analgesic drugs on the uptake and release of neurotransmitters in nerve-ending preparations isolated from rat brain was studied. The uptake of 14C-dopamine into rat striatal synaptosomes and of 14C-norepinephrine into hypothalamic synaptosomes was inhibited by morphine in concentrations of 10-5 and 10-4 M, respectively. Kinetic analyses of dopamine uptake in the presence of morphine suggested that low affinity uptake was inhibited rather than high affinity uptake. Narcotic drugs had no direct effect on catecholamine release. The release of 14C-acetylcholine from 14C-choline-precharged striatal synaptosomes was inhibited by 10-4 and higher concentrations of morphine. The intrasynaptosomal synthesis of 14C-acetylcholine from 14C-choline was also inhibited by the same concentration of morphine. Other opioids also inhibited the release of newly synthesized 14C-acetylcholine from striatal synaptosomes in concentrations of 10-5 M or higher. Levorphanol at 10-5 M concentration inhibited 14C-acetylcholine release, while its less active isomer, dextrorphan, did not inhibit release at this concentration, thus separating the effects of narcotic agonists by activity. However, another pair of isomers, levo-and dextro-methadone, were almost equally active as inhihitors of acetylcholine release from striatal nerve-ending preparations.
Footnotes
- Received March 21, 1973.
- Accepted September 24, 1973.
- © 1974 by The Williams & Wilkins Co.
JPET articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|
