Neurosteroid enhances glutamate release in rat prelimbic cortex via activation of alpha1-adrenergic and sigma1 receptors.
The present paper studied the effect and mechanism of neurosteroid pregnenolone sulfate (PREGS) on spontaneous glutamate release using electrophysiological and biochemical methods combined with a pharmacological approach. The results suggested that PREGS had a selective enhancing effect on spontaneous glutamate release in the prelimbic cortex and the hippocampus but not in the striatum. The effect of PREGS in the prelimbic cortex appeared to be via modulation of alpha1-adrenergic and sigma1 receptors, but in the hippocampus it might be dependent on sigma1 receptors only. The activation of alpha1-adrenergic receptors synergized sigma1 receptor activation in the prelimbic cortex. Intracellular calcium released from the endoplasmic reticulum, protein kinase C, adenylyl cyclase and protein kinase A played a key role in the effect of PREGS. Intracellular calcium, protein kinase C and adenylyl cyclase might be upstream events in the activation of protein kinase A after PREGS.
Dong
Y
Y
State Key Laboratory of Medical Neurobiology, Fudan University Shanghai Medical College, Shanghai, 200032, People's Republic of China.
Fu
Y-M
YM
Sun
J-L
JL
Zhu
Y-H
YH
Sun
F-Y
FY
Zheng
P
P
D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000502:physiology; D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000502:physiology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology; D004594:Electrophysiology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008954:Models, Biological; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000494:pharmacology; D011284:Pregnenolone / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology*; D017480:Receptors, sigma / Q000037:antagonists & inhibitors / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D000097605:Sigma-1 Receptor
D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases; D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D002118:Calcium; D017868:Cyclic AMP-Dependent Protein Kinases; D018698:Glutamic Acid; D018377:Neurotransmitter Agents; D011284:Pregnenolone; D011493:Protein Kinase C; D018340:Receptors, Adrenergic, alpha-1; D017480:Receptors, sigma; D000097605:Sigma-1 Receptor; C018370:pregnenolone sulfate