Activation of phosphatidylinositol-linked D1-like receptors increases spontaneous glutamate release in rat somatosensory cortical neurons in vitro.
Central dopaminergic system exerts profound modulation on spontaneous glutamate release in various brain regions mainly through D(1) receptor/cAMP/PKA pathway. It remains unclear whether the phosphatidylinositol (PI)-linked D(1)-like receptors are also involved in such modulatory actions. The identification of substituted phenylbenzazepine SKF83959 as the selective agonist for the atypical D(1)-like receptors has given impetus to study their influence on the spontaneous glutamate release in the brain. In the present study the effects of SKF83959 on the spontaneous excitatory postsynaptic currents (sEPSCs) were investigated through whole-cell recording from layer V-VI pyramidal neurons in rat somatosensory cortical slices. Perfusion with SKF83959 (10-100 microM) considerably increased the frequency of sEPSCs, while had no significant effect on the amplitude of sEPSCs. The increase of sEPSC frequency by SKF83959 was blocked by SCH23390, a D(1)-like receptor antagonist, but not by the antagonists for D(2) receptor, alpha(1)-adrenoceptor and 5-HT(2A/2C) receptor. U-73122 (PLCbeta inhibitor), 2-APB (IP(3) receptor antagonist), chelerythrine chloride (PKC inhibitor) and capsazepine (TRPV1 antagonist) could block the effects of SKF83959, whereas H-89 (PKA inhibitor) and forskolin (adenylyl cyclase activator) had no effect. Taken together, sensitization of TRPV1 channels by PKC after activation of D(1) receptor/PLCbeta signaling pathway mediated SKF83959-induced increase in the sEPSC frequency. To our knowledge, this is the first pharmacological evidence that PI-linked D(1)-like dopamine receptors do exist in presynaptic terminals of cortical neurons and play an important role in controlling the spontaneous glutamate release.
Chu
Hong-Yuan
HY
State Key Laboratory of Drug Research and Department of Pharmacology II, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Yang
Zhi
Z
Zhao
Bin
B
Jin
Guo-Zhang
GZ
Hu
Guo-Yuan
GY
Zhen
Xuechu
X
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D018698:Glutamic Acid / Q000378:metabolism*; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009924:Organ Culture Techniques; D010716:Phosphatidylinositols / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000819:agonists / Q000378:metabolism*; D013003:Somatosensory Cortex / Q000187:drug effects / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D001552:Benzazepines; D018491:Dopamine Agonists; D010716:Phosphatidylinositols; D017447:Receptors, Dopamine D1; C534628:SCH 23390; D018698:Glutamic Acid; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; C080703:SK&F 83959