Metabolism of [3H]Nipecotic Acid in the Rabbit Retina

Nipecotic acid has been demonstrated to block the gamma-aminobutyric acid transport systems. Previous studies have shown that the uptake system is the first transmitter-specific parameter to appear during the development of the rabbit retina. Use of these observations has been made to study the influence on the development of gamma-aminobutyric acid receptors of altering the uptake mechanism by treating newborn pups with nipecotic acid to block GABA transport. The present study of the in vivo metabolism of [3H]nipecotic acid in the CNS measured the changes in the levels of [3H]nipecotic acid in both adult and newborn rabbit retinas after injection of the label into the vitreal chamber. It was found that the effective half-life of [3H]nipecotic acid in the vitreous is about 5 h for adult tissue and 3 h for newborn. In contrast, all retinal fractions retained the label longer, the effective half-lives being about 60 h (adult) and 45 h (newborn). Further, no labeled metabolites of nipecotic acid were detected in either adult or newborn tissue. This study gives evidence that the degradation of nipecotic acid in nervous tissue is minimal and suggests that, although the rate of clearance is faster in neonates, the fate of nipecotic acid in vivo may be similar in both adult and newborn tissues.     

Chloride Ions Preferentially Mask High-Affinity GABA Binding Sites

Chloride ions (Cl-) act to regulate the appearance of gamma-aminobutyric acid (GABA) binding sites in synaptic membranes from bovine retinas. Scatchard analysis indicates that the presence of Cl- results in a preferential decrease (85%) in the number of high-affinity binding sites, with no statistically significant change in the affinity (KD) of either the high- or low-affinity sites. The finding that the appearance of this binding site is altered by the presence of Cl- may indicate that Cl- acts, either directly or indirectly, to regulate the appearance, and hence function, of the high-affinity GABA receptor.