Regulation of 3HNorepinephrine Release by Opioids in Human Cerebral Cortex

To investigate the receptors mediating the regulation of norepinephrine (NE) release in human cerebral cortex slices, we examined the effects of opioid agonists for mu-, delta-, and kappa -receptors on the high potassium (15 mM) -evoked release of [3H]NE. [3H]NE release induced by high potassium was calcium-dependent and tetrodotoxin-sensitive. [D-Pen2, D-Pen5]enkephalin (DPDPE) and deltorphin II (Delt II) inhibited the stimulated release of norepinephrine in a dose-dependent manner. However, Tyr-D-Ala-Gly- (Me) Phe-Gly-ol and U69, 593 did not influence the NE release. Inhibitory effect of DPDPE and Delt-II was antagonized by naloxone, naltrindole, 7-benzylidenaltrexone and naltriben. These results suggest that both delta 1 and delta 2 receptors are involved in regulation of NE release in human cerebral cortex.

The Effect of Ketamine on Norepinephrine Release in the Rat Hippocampus / 대한마취과학회지

BACKGREOUND: Since it has been reported that ketamine, an intravenous anesthetic, is a non-competitive antagonist of N-methyl-D-aspartic acid (NMDA) receptors, a large number of experimental data on the several mechanism of this process have been accumulated. But the mechanism about the effect of ketamine on neurotransmitter release in central nervous system has not been clearly elucidated yet. Therefore the present study was undertaken to investigate the effects of ketamine and thiopental sodium on hippocampal norepinephrine (NE) release, and also to examine the relationship between ketamine and NMDA receptor mechanisms in the rat hippocampus. METHODS: Slices from rat hippocampus were equilibrated with [3H]norepinephrine ([3H]NE) and the release of labelled products was evoked by electrical stimulation (3 Hz, 5 V/cm, 2 ms, rectangular pulses, 2 min), and the influence of various agents on the evoked tritium-outflow and the basal rate of release were investigated. RESULTS: In rat hippocampal slices, ketamine (1~30 micrometer) and thiopental sodium (1~30 micrometer) did not affect the evoked NE release and the basal release in the normal and Mg2 free medium. NMDA (3~100 micrometer) did not alter the NE release in the normal medium, but NMDA (1~30 micrometer) increased the basal rate of NE release in the Mg2 free medium. The increasing effects of NMDA on basal release were completely abolished by ketamine treatment in a concentration dependent manner. But, thiopental sodium did not affect the NMDA effect. CONCLUSIONS: These results suggest that increment of the basal rate of NE release is mediated by NMDA receptor in the rat hippocampus and ketamine completely block this effect, but thiopental sodium is not involved in these process.

Role of nitric oxide in ischemia-evoked release of norepinephrine from rat cortex slices

It has been generally accepted that glutamate mediates the ischemic brain damage, excitotoxicity, and induces release of neurotransmitters, including norepinephrine (NE), in ischemic milieu. In the present study, the role of nitric oxide (NO) in the ischemia-induced (3H)norepinephrine((3H)NE) release from cortex slices of the rat was examined. Ischemia, deprivation of oxygen and glucose from Mg2+/-free artificial cerebrospinal fluid, induced significant release of (3H)NE from cortex slices. This ischemia-induced (3H)NE release was significantly attenuated by glutamatergic neurotransmission modifiers. NG-nitro-L-arginine methyl ester (L-NAME), NG-monomethyl-L-arginine (L-NMMA) or 7-nitroindazole, nitric oxide synthase inhibitors attenuated the ischemia-evoked (3H)NE release. Hemoglobin, a NO chelator, and 5, 5-dimethyl-L-pyrroline-N-oxide (DMPO), an electron spin trap, inhibited (3H)NE release dose-dependently. Ischemia-evoked (3H)NE release was inhibited by methylene blue, a soluble guanylate cyclase inhibitor, and potentiated by 8-bromo-cGMP, a cell permeable cGMP analog, zaprinast, a cGMP phosphodiesterase inhibitor, and S-nitroso-N-acetylpenicillamine (SNAP), a nitric oxide generator. These results suggest that the ischemia-evoked (3H)NE release is mediated by NMDA receptors, and activation of NO system is involved.