INACTIVITY OF PHOSPHOETHANOLAMINE, AN ENDOGENOUS GABA ANALOG DECREASED IN ALZHEIMERS-DISEASE, AT GABA BINDING-SITES

Phosphoethanolamine (PE) is a metabolite of phospholipid metabolism wh ich is decreased in Alzheimer's disease brain. PE shows a strong struc tural similarity to the inhibitory neurotransmitter, GABA, and the GAB A(B) receptor partial agonist, 3-amino-propylphosphonic acid. The abil ity of PE to compete for binding to GABA(A) and GABA(B) binding sites was investigated. GABA(A) sites were studied using [H-3]SR-95531 and [ H-3]muscimol. GABA(B) sites were studied using [H-3]GABA in the presen ce of isoguvacine to saturate GABA(A) sites. Total [H-3]GABA binding w as also examined. PE showed little activity at any of the GABA binding sites investigated. PE was most potent at GABA(B) sites, but the IC50 of 7.5 +/- 0.75 mM was considerably higher than its maximal physiolog ic concentration of approximately 1.5 mM. The efficient exclusion of P E from GABA binding sites may be an important physiologic mechanism in the control of inhibitory neurotransmission. The structural basis for this exclusion is discussed in reference to the GABA(B) partial agoni st 3-amino-propylphosphonic acid.