Inhibition of GABAB receptor binding by guanyl nucleotides

GTP and GDP decreased the saturable binding of [3H]baclofen or [3H]gamma-aminobutyric acid ( [3H]GABA) to GABAB but not GABAA receptors whereas GMP displayed negligible activity. This effect was specific to guanyl nucleotides and was not mimicked by high concentrations of ATP. The inhibition of ligand binding was the result of a diminished receptor affinity with no change in receptor number. The use of a complete physiological saline solution rather than Tris buffer plus Ca2+ or Mg2+ increased the potency of GTP at the GABAB receptor. The results are discussed in relation to the effects of GABA and GTP on adenylate cyclase activity in the brain.