l-Stepholidine increases the frequency of sEPSC via the activation of D1 dopamine signaling pathway in rat prelimbic cortical neurons.
OBJECTIVE
To investigate the effect of l-stepholidine (SPD) on the frequency of spontaneous excitatory postsynaptic currents (sEPSC) in the pyramidal cells between layers V and VI in the prelimbic cortex (PL).


METHODS
A whole-cell patch clamp in rat brain slices was used.


RESULTS
SPD significantly increased the frequency of sEPSC in a concentration-dependent manner. A selective D1 dopamine receptor antagonist SCH23390 blocked SPD-mediated effects, whereas the D1 agonist SKF38393, but not the D2/3 antagonist sulpiride, mimicked SPD-mediated increase in the frequency of sEPSC. Moreover, both protein kinase A (PKA) inhibitor N-(2- [p-bromocinnamylamino]-ethyl)-5-isoquinolinesulfonamide hydrochloride and protein kinase C (PKC) inhibitor chelerythrine attenuated the effect of SPD on sEPSC.


CONCLUSIONS
SPD elicits its effect on the frequency of sEPSC on the PL pyramidal cells via presynaptic D1 receptors, and is dependent on PKA and PKC signaling pathways.
Gao
Ming
M
Department of Pharmacology, State Key Laboratory of Drug Research, Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 201203, China.
Liu
Chang-Liang
CL
Yang
Shen
S
Zhen
Xue-Chu
XC
Jin
Guo-Zhang
GZ
D000818:Animals; D001599:Berberine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D018491:Dopamine Agonists / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*
D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D017447:Receptors, Dopamine D1; D001599:Berberine; C010513:stepholidine; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D004298:Dopamine