Neurosteroid pregnenolone sulfate inhibits stimulus-evoked EPSC via presynaptic inhibition of protein kinase A in rat prelimbic cortical neurons.
Pregnenolone sulfate is one of the most abundantly produced neurosteroids in the brain. The present paper studies the effect of pregnenolone sulfate on excitatory synaptic transmission in the pyramidal cells of the layer V-VI of the prelimbic cortex using whole-cell patch-clamp in slices. We found that pregnenolone sulfate inhibited stimulus-evoked excitatory postsynaptic currents (EPSC); the effect of pregnenolone sulfate was significant at concentration of 1 microM and increased with an increase in concentrations; pregnenolone sulfate had no effect on the amplitude and frequency of miniature excitatory spontaneous postsynaptic currents; pregnenolone sulfate significantly enhanced the paired-pulse facilitation (PPF) and inhibited dopamine and 5-HT-evoked increase in the frequency of spontaneous excitatory postsynaptic currents; the protein kinase A inhibitor H89 and Rp-cAMPS enhanced PPF and canceled the effect of pregnenolone sulfate on PPF; pregnenolone sulfate inhibited the protein kinase A agonist forskolin-evoked increase in the frequency of spontaneous excitatory postsynaptic currents; the G(i) protein inhibitor N-ethylmaleimide canceled the effect of pregnenolone sulfate on PPF. These results suggest that pregnenolone sulfate inhibits stimulus-evoked EPSC via presynaptic inhibition of protein kinase A in rat prelimbic cortical neurons.
State Key Laboratory of Medical Neurobiology, Fudan University Shanghai Medical College, 138 Yixueyuan Road, Shanghai 200032, PR China.
Jian-Li
JL
Sun
Yan-Lian
YL
Dong
Ying-Mei
YM
Fu
Yan-Hua
YH
Zhu
Yi
Y
Dong
Ping
P
Zheng
D000818:Animals; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects*; D005576:Colforsin / Q000037:antagonists & inhibitors; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors*; D018492:Dopamine Antagonists / Q000494:pharmacology; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005033:Ethylmaleimide / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects*; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000037:antagonists & inhibitors; D066298:In Vitro Techniques; D008032:Limbic System / Q000166:cytology / Q000187:drug effects*; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D011284:Pregnenolone / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D017729:Presynaptic Terminals / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000187:drug effects; D012702:Serotonin Antagonists / Q000494:pharmacology
D018492:Dopamine Antagonists; D004791:Enzyme Inhibitors; D018091:Receptors, AMPA; D012702:Serotonin Antagonists; D005576:Colforsin; D011284:Pregnenolone; D017868:Cyclic AMP-Dependent Protein Kinases; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D005033:Ethylmaleimide