The actions of 3-aminopropanephosphinic acid at GABAB receptors in rat hippocampus.
The actions of 3-aminopropanephosphinic acid (APPA) were examined using whole-cell patch-clamp recording in rat hippocampal slice. In recordings from neurons in subfield CA1 of slices from young (2-4 weeks) and adult (greater than 2 month) rats, APPA (0.5-50 microM) produced membrane hyperpolarization and outward current under voltage-clamp. APPA also inhibited excitatory postsynaptic potentials with an IC50 of 2.3 microM, and reduced inhibitory postsynaptic potentials at concentrations from 0.1 to 1 microM. The hyperpolarizing and synaptic depressant effects of APPA were reduced by 2-OH-saclofen an antagonist at the B-type receptor for the neurotransmitter gamma-aminobutyric acid (GABA). In this preparation APPA exhibited potencies similar to those previously reported for the GABAB receptor agonist baclofen. APPA was much less effective in inhibiting synaptic transmission measured using field potential recordings. The observations made with whole-cell patch-clamp recording indicate that in hippocampus APPA acts as a potent agonist at presynaptic GABAB receptors associated with both excitatory and inhibitory synapses, and also activates postsynaptic GABAB receptors.
Lovinger
D M
DM
Section of Electrophysiology, LPPS, National Institute on Alcohol Abuse and Alcoholism, Rockville, MD 20852.
Harrison
N L
NL
Lambert
N A
NA
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000375:Aging / Q000502:physiology; D000818:Animals; D001418:Baclofen / Q000031:analogs & derivatives / Q000494:pharmacology; D018756:GABA Antagonists; D006624:Hippocampus / Q000187:drug effects* / Q000648:ultrastructure; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009943:Organophosphorus Compounds / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000502:physiology; D013569:Synapses / Q000502:physiology / Q000648:ultrastructure; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D018756:GABA Antagonists; D009943:Organophosphorus Compounds; D011963:Receptors, GABA-A; C061388:3-aminopropylphosphinic acid; D001418:Baclofen; C057491:2-hydroxysaclofen