Actions of (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD) in retinal ON bipolar cells indicate that it is an agonist at L-AP4 receptors.
Metabotropic glutamate receptors (mGluRs) include receptors sensitive to L-2-amino-4-phosphonobutyrate (L-AP4) and 1S,3R-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD). To determine whether 1S,3R-ACPD is an agonist at retinal L-AP4 receptors, whole cell voltage clamp recordings were obtained from mudpuppy ON bipolar cells in a superfused retinal slice and L-AP4 and 1S,3R-ACPD were bath applied. Both compounds evoked similar outward currents which reversed near 0 mV and were accompanied by an increased input resistance. Responses to both agonists washed out in parallel suggesting they act through the same second messenger pathway(s). Inhibitors of cGMP-PDE activity suppressed responses to both L-AP4 and 1SR,3RS-ACPD, suggesting that both compounds activate cGMP-PDE. Responses to 1S,3R-ACPD were occluded by prior activation of L-AP4 receptors, but not blocked by the non-AP4, mGluR antagonists, L-aminophosphonopropionic acid (L-AP3) or 4-carboxy-3-hydroxyphenylglycine (4C3H-PG). These results indicate that 1S,3R-ACPD is an agonist at L-AP4 receptors. 1S,3S-ACPD and 4C3H-PG evoked outward currents similar to L-AP4 suggesting they may also be L-AP4 receptor agonists. Using the b-wave of the ERG as an assay for ON bipolar cell responses, concentration/response curves were obtained for ACPD enantiomers. The rank-order potency of ACPD enantiomers at L-AP4 receptors in ON bipolar cells is similar to their rank-order potency at non-AP4, mGluRs in brain which suggests that the receptors possess similar binding sites and may be members of a common receptor family.
Thoreson
W B
WB
Department of Physiology, University of Minnesota, Minneapolis 55455.
Miller
R F
RF
D000613:Aminobutyrates / Q000494:pharmacology; D000818:Animals; D003515:Cycloleucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D058785:GABA-A Receptor Agonists; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D009338:Necturus maculosus / Q000502:physiology*; D011963:Receptors, GABA-A / Q000032:analysis / Q000502:physiology; D017470:Receptors, Glutamate / Q000502:physiology; D012160:Retina / Q000737:chemistry / Q000166:cytology* / Q000187:drug effects
D000613:Aminobutyrates; D018690:Excitatory Amino Acid Agonists; D058785:GABA-A Receptor Agonists; D011963:Receptors, GABA-A; D017470:Receptors, Glutamate; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; C078245:4-carboxy-3-hydroxyphenylglycine; C012729:2-amino-4-phosphonobutyric acid; D005998:Glycine