3H-metaraminol releasing action of mescaline from rat hypothalamus in vitro
Om D. Gulati, Nandkumar S. Shah
European Journal of Pharmacology November 15, 1977 DOI: 10.1016/0014-2999(77)90249-7 via Elsevier
Summary
AI-generated from the abstractMescaline releases a radioactive tracer (3H-metaraminol) from isolated rat hypothalamus tissue in a dose-dependent manner, acting through two distinct mechanisms: a calcium-independent pathway similar to tyramine and a calcium-dependent pathway sensitive to lidocaine. Cocaine does not affect this release, and removing calcium from the medium does not block mescaline's effect, whereas high potassium-induced release requires calcium. Tetrodotoxin and lidocaine partially block mescaline's action but fully block potassium-induced release. Prior exposure to tyramine reduces mescaline's releasing effect. Mescaline itself is poorly retained by storage particles in the tissue.
Study at a glance
| Characteristics | In vitro experiment Peer reviewed |
|---|---|
| Population | Rat isolated hypothalamus |
| Interventions | Mescaline Cocaine Tetrodotoxin Lidocaine Tyramine |
| Dose | 4 x 10(-4) M mescaline, 3 x 10(-5) M cocaine, 3 x 10(-7) M tetrodotoxin, 6 x 10(-5) M lidocaine, 3 x 10(-4) M tyramine, 6 x 10(-2) M KCl |
| Duration | 50 min of efflux |
| Key finding | Mescaline releases 3H-metaraminol from rat hypothalamus via both calcium-independent (tyramine-like) and calcium-dependent (lidocaine-sensitive) mechanisms. |
Abstract
The amine releasing action of mescaline was investigated in rat isolated hypothalamus labeled with 3H-metaraminol. Mescaline had no effect on the uptake of 3H-metaraminol but produced its release in a concentration-related manner. 4 x 10(-4) M mescaline, which produced submaximal effects was used for subsequent experiments. 3 x 10(-5) M cocaine had no effect on the 3H-metaraminol releasing action of mescaline. Mescaline was fully effective in Ca2+-free medium while 6 x 10(-2) M KCl was ineffective. 3 x 10(-7) M tetrodotoxin or 6 x 10(-5) M lidocaine partially blocked mescaline-induced release but substantially or completely blocked 3 x 10(-2) M KCl-induced release. Prior exposure of hypothalamus to 3 x 10(-4) M tyramine reduced the releasing action of mescaline. Thus, mescaline appears to release 3H-metaraminol both by Ca2+-independent (tyramine-like) and Ca2+-dependent (lidocaine-sensitive) mechanisms. 3 x 10(-4) M tyramine and 6 x 10(-2) M KCl released 14C from control hypothalamus labelled with 14C-mescaline, but not from reserpinized hypothalamus. The amounts of 14C recovered in 14C-mescaline labeled control and reserpinized hypothalamus at the end of 50 min of efflux were similar suggesting a poor retention of 14C-mescaline by storage particles.