Potentiation of synaptic transmission by (S)-3,5-dihydroxy phenylglycine in the rat dentate gyrus in vitro: a role for voltage dependent calcium channels and protein kinase C.
1. The authors have previously shown that direct activation of metabotropic glutamate receptors (mGluRs) by (S)-3,5-dihydroxyphenylglycine ((S)-DHPG) can induce a long-lasting potentiation of synaptic transmission in the rat dentate gyrus in vitro. Here the authors provide further characterisation of this agonist-induced potentiation. 2. Field excitatory post-synaptic potentials were recorded from the denate gyrus of rat hippocampal slices prepared by standard methods. 3. (S)-DHPG (40 microM) induced a significant potentiation of the field EPSP slope (148.6 +/- 4.3% compared to controls, n = 5), which occluded tetanically-induced LTP. 4. This potentiation was inhibited by the PKC inhibitors staurosporine (0.1 microM) and H-7 (100 microM) and by the voltage dependent Ca2+ channel (VDCC) blockers NiCl2 (50 microM) and nifedipine (20 microM). 5. The mGluR5 specific agonist (RS)-2-Chloro-5-Hydroxyphenylglycine (CHPG) did not induce a potentiation when applied to slices at concentrations from 20 microM to 1 mM indicating that the (S)-DHPG potentiation may be mediated through group I subtype 1 mGluRs. 6. In conclusion the (S)-DHPG-induced potentiation observed in our studies may be PKC dependent and is likely to be mediated through both T/L subtype VDCC and mGluR1 subtype receptors.
O'Leary
D M
DM
Department of Human Anatomy and Physiology, University College, Earlsfort Terrace, Dublin 2, Ireland.
O'Connor
J J
JJ
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D018891:Dentate Gyrus / Q000187:drug effects*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology; D010648:Phenylacetates / Q000494:pharmacology*; D011493:Protein Kinase C / Q000187:drug effects / Q000502:physiology; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000187:drug effects*; D012118:Resorcinols / Q000494:pharmacology*; D009435:Synaptic Transmission / Q000187:drug effects*
C107349:2-chloro-5-hydroxyphenylglycine; D002121:Calcium Channel Blockers; D018691:Excitatory Amino Acid Antagonists; D010648:Phenylacetates; D018094:Receptors, Metabotropic Glutamate; D012118:Resorcinols; C079215:3,5-dihydroxyphenylglycine; D011493:Protein Kinase C; D005998:Glycine