Possible presynaptic actions of 2-amino-4-phosphonobutyrate in rat olfactory cortex

Br J Pharmacol. 1987 Aug;91(4):753-61. doi: 10.1111/j.1476-5381.1987.tb11273.x.

Abstract

1 The effect of 2-amino-4-phosphonobutyrate (APB) on facilitation at the lateral olfactory tract (LOT)-superficial pyramidal cell synapse of the olfactory cortex has been studied by recording the relative changes in amplitude of the N-waves evoked on stimulation of the LOT by pairs of stimuli. 2 Although APB (0.01 to 5 mM) reduced the amplitude of the conditioning response there was an overall increase in facilitation over conditioning intervals of up to 1700 ms which was concentration-dependent and inversely related to the concentration of extracellular calcium (1.25 to 5 mM). 3 The L-(+)-isomer of APB was more potent than the D-(-)-form in increasing synaptic facilitation. 4 The potassium channel blockers 4-aminopyridine (0.25 mM), 3,4-diaminopyridine (0.1 mM), tetraethylammonium (10 mM) and catechol (1 mM) all reduced facilitation but failed to antagonize the increase in facilitation produced by APB (1 mM). In contrast, all 4 drugs antagonized APB-induced reductions in the amplitude of the conditioning response. 5 APB (1 mM) significantly reduced the K+-evoked release of endogenous aspartate and glutamate but not of gamma-aminobutyric acid from slices of olfactory cortex. 6 It is suggested that APB reduces the amplitude of the conditioning response and increases synaptic facilitation by reducing transmitter release from the LOT terminals. The mechanism is unlikely to involve activation of terminal potassium currents.

MeSH terms

  • Amino Acids / metabolism
  • Aminobutyrates / pharmacology*
  • Animals
  • In Vitro Techniques
  • Ion Channels / drug effects
  • Male
  • Olfactory Bulb / drug effects*
  • Olfactory Bulb / metabolism
  • Potassium / pharmacology
  • Rats
  • Rats, Inbred Strains
  • Synapses / drug effects*

Substances

  • Amino Acids
  • Aminobutyrates
  • Ion Channels
  • 2-amino-4-phosphonobutyric acid
  • Potassium