The D1 dopamine receptor agonist SKF-38393 stimulates the release of glutamate in the hippocampus.
The present study was undertaken to better assess the role of dopamine on exocytosis. Since direct activation of adenylate cyclase (e.g., with forskolin) enhances neurotransmitter release it was of interest to see whether the activation of D1-type dopamine receptors, which are positively coupled to adenylate cyclase, could also modulate the molecular machinery underlying the fusion of synaptic vesicles and the release of neurotransmitter. To answer this question we have looked at the effect of the D1-type dopamine receptor agonist SKF-38393 on the spontaneous release of glutamate from cultured rat hippocampal neurons. SKF-38393 enhanced the frequency but not the amplitude of tetrodotoxin-resistant excitatory postsynaptic currents which argues for a presynaptic locus of D1 action. This effect was blocked by the D1-dopaminergic receptor antagonist SCH-23390 and the protein kinase A inhibitors H-7 and Rp-cAMP whereas pertussis toxin failed to affect the dopaminergic response. In addition, carbachol and Ruthenium Red also stimulated exocytosis but did not occlude the SKF-38393-induced modulation. These results indicate that SKF-38393 presynaptically enhances the release of glutamate via a pertussis toxin-insensitive and protein kinase A-dependent mechanism, which most likely involves D1-type dopamine receptors. Our results underline the importance of protein kinase A as potent modulator of synaptic transmission and suggest that high concentrations of dopamine can greatly enhance the release of glutamate in the hippocampus.
Bouron
A
A
Department of Pharmacology, University of Bern, Switzerland.
Reuter
H
H
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology*; D000818:Animals; D005576:Colforsin / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology*; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism*; D051381:Rats; D017447:Receptors, Dopamine D1 / Q000819:agonists* / Q000502:physiology; D013779:Tetrodotoxin / Q000494:pharmacology
D018491:Dopamine Agonists; D017447:Receptors, Dopamine D1; D005576:Colforsin; D018698:Glutamic Acid; D013779:Tetrodotoxin; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine