ACTIVATION OF GLYCOGEN-PHOSPHORYLASE BY SEROTONIN AND 3,4-METHYLENEDIOXYMETHAMPHETAMINE IN ASTROGLIAL-RICH PRIMARY CULTURES - INVOLVEMENT OF THE 5-HT2A RECEPTOR

被引：47

作者：

POBLETE, JC

AZMITIA, EC

机构：

[1] Department of Biology, New York University, New York, NY 10003, 100 Washington Sq. East

来源：

BRAIN RESEARCH | 1995年 / 680卷 / 1-2期

关键词：

GLYCOGEN PHOSPHORYLASE; SEROTONIN; ASTROCYTE; 3,4-METHYLENEDIOXYMETHAMPHETAMINE; GLYCOGEN; METABOLISM;

D O I：

10.1016/0006-8993(95)00201-Z

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Neurotransmitters, neuropeptides, and ions regulate glycogen levels in the brain by modulating the activity of glycogen synthase (GSase) and glycogen phosphorylase (GPase). GPase is co-localized with glial fibrillary acidic protein (GFAP), an astroglia-specific marker, suggesting that glycogen is localized in astroglial cells. Additionally, functional serotonin (5-HT) receptors are found in both neurons and glia, and 5-HT is known to stimulate glycogenolysis. It is reported that 3,4-methylene-dioxymethamphetamine (MDMA), a drug of abuse, stimulates the release and inhibits the reuptake of 5-HT, and selectively inhibits the activity of (MDMA. These biochemical consequences of MDMA lead to increased extra-cellular 5-HT levels. This study investigates the effects of MDMA(+) and serotonin (5-HT) on glycogen metabolism in the rat brain. A histochemical method was designed to visualize active glycogen phosphorylase (GPase) in an astroglial-rich primary culture. Serotonin activated GPase in a concentration-dependent manner (100 nM-100 mu M). Maximal activation by 5-HT was achieved by 50 mu M and resulted in a 167% increase in the number of reactive sites (P < 0.001). MDMA(+) (500 nM-50 mu M) directly stimulated GPase activity with maximal activation induced by 5 mu M, which caused a 70% increase in the number of reactive sites (P < 0.001). The 5-HT2 receptor agonist, 1-(2,5-dimethoxy-4-bromophenyl)-2-aminopropane (DOB), also displayed a concentration-dependent increase in the number of GPase reactive sites. Maximal stimulation by DOE occurred at 100 nM which increased the number of reactive sites by 166% (P < 0.001). These effects of 5-HT and MDMA(+) were significantly attenuated by mianserin (200 nM), a 5-HT2 receptor antagonist. An astrocyte-neuron metabolic link may be vital for synaptic homeostasis. By increasing 5-HT levels in the synapse, MDMA(+) may increase GPase activity and promote glycogenolysis via activation of the 5-HT2 receptor. Prolonged GPase activity may lead to depletion of synaptic energy stores, thereby compromising the energy state of the synapse. The resulting deficiency in synaptic energy may contribute to terminal degeneration induced by substituted amphetamines.

引用

页码：9 / 15

页数：7

共 39 条

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