Phenylglycine derivatives antagonize the excitatory response to Purkinje cells to 1S,3R-ACPD: an in vivo and in vitro study.
The interactions of the phenylglycine derivatives (S)-4-carboxyphenylglycine (S-4CPG) and (R,S)-alpha-methyl-4-carboxyphenylglycine (MCPG) with responses of rat cerebellar Purkinje cells to (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD) were examined by intracellular recordings in acute cerebellar slices and extracellular recordings in vivo, using multibarrel electrodes. In vitro, both S-4CPG (100 microM to 1 mM) and MCPG (250 microM to 1 mM) reversibly and dose-dependently reduced an inward current induced by bath-applied 1S,3R-ACPD, an agonist at metabotropic glutamate receptors (mGluRs), in Purkinje cells voltage-clamped at -60 to -65 mV. S-4CPG applied at a concentration of 1 mM reduced the 1S,3R-ACPD induced current to 17% of control values but when applied alone also produced an inward current amounting to 26.8% of that induced by 1S,3R-ACPD. MCPG bath-applied at 250 microM, 500 microM, or 1 mM reduced the 1S,3R-ACPD-induced current to 85%, 56% or 3% of control values, respectively, and did not cause any current when applied alone even at a concentration of 1 mM. In vivo, iontophoretic application of 1S,3R-ACPD induced a transient increase followed by a decrease in the firing rate of Purkinje cells. The excitatory response of Purkinje cells to 1S,3R-ACPD was suppressed during ejection of either one of the phenylglycine derivatives, while the mechanism resulting in the decreased firing rate was not affected. Our observations demonstrate that both S-4CPG and MCPG antagonized the excitatory response of cerebellar Purkinje cells to 1S,3R-ACPD.(ABSTRACT TRUNCATED AT 250 WORDS)
Lingenhöhl
K
K
Research and Development Department, Ciba-Geigy Ltd., Basel, Switzerland.
Olpe
H R
HR
Bendali
N
N
Knöpfel
T
T
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001565:Benzoates / Q000494:pharmacology; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects; D003515:Cycloleucine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004594:Electrophysiology; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D066298:In Vitro Techniques; D007478:Iontophoresis; D008297:Male; D009498:Neurotoxins / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D011689:Purkinje Cells / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors
D001565:Benzoates; D009498:Neurotoxins; D018094:Receptors, Metabotropic Glutamate; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; C079694:alpha-methyl-4-carboxyphenylglycine; C079693:4-carboxyphenylglycine; D005998:Glycine