J Korean Soc Endocrinol.
1994 Jun;10(2):115-124.
Effects of Diaxoxide, Cromakalim and Pinacidil on Acetylcholine and Norepinephrine Release in Rat Hippocampus
Abstract
- It is aim of the present study to gain more insight into the role K_ATP-channel in acetylcholine(Ach) and norepinephrine(NE) release in the central nervous system. Slices from the rat hippocampus were equilibrated with [^3H]-choline and [^3H]-norepinephrine and the release of the labelled products was evoked by electrical stimulation(3 Hz, 2 ms, 5 VCm^-1, rectangular pulses, 2 min), and the influence of K_ATP-channel openers and other related drugs on the evoked tritium-outflow was investigated.Cromakalim, in concentrations ranging from 10 to 300 uM, decreased the evoked [^3H]-Ach & [^3H]-NE release in a dose-dependent manner without changing the basal rate of release. Diazoxide(10-300uM) inhibited the evoked[^3H]-NE release but increased the evoked [^3H]-Ach release significantly, while, the effects of pinacidil(3-100uM) were vice versa. Glibenclamide(1-30uM), a selective K_ATP-channel blocker, did not affect the evoked or basal release of both tritium outflow. And the inhibitory effect of K^+-channel openers was inhibited by glibenclamide pretreatment. Pinacidil-induced increase in the evoked NE release was not affected by cocaine, but potentiated by hydrocortisone. And the diazoxide-induced increase in Ach release was not affected by hydrocortisone pretreatment.These results suggest that ATP-sensitive K^+ -channels are present in the both adrenergic and cholinergic nerve endings of rat hippocampus, but these channels seem to be pharmacologically different from those reported for smooth muscle cells and pancreatic beta-cells.