Uptake and receptor sites for glycine in isolated bovine adrenal medulla chromaffin cells.

[3H]Glycine is actively taken up into bovine isolated adrenal medulla chromaffin cells with the subsequent catecholamine release. [3H]Glycine uptake has two interaction sites based on relative Km measurements. These sites are inherently distinct since the effects of strychnine and temperature on glycine binding are significantly different. The high affinity site (Km = 6 x 10(-7) M) is strychnine-sensitive and its activity is unaltered at 4 degrees C. These results point to a receptor-like function. The low-affinity site (Km = 1.4 x 10(-3) is strychnine-insensitive and is significantly inhibited (75%) by low temperature (4 degrees C), by low Na+ concentration and 50% by ouabain (10(-4) M). Compounds structurally similar to glycine and known to antagonize its uptake to neuronal cells, such as beta-alanine, N-methyl-d,l-alanine and sarcosine, also inhibit the low affinity site which indicate a glycine uptake function for this site. The relative activity of the uptake inhibitors indicate that in the adrenal chromaffin cell, glycine uptake is carried out by a System A amino acid transporter mechanism. GABA does not affect glycine binding or uptake in the chromaffin cells, suggesting that these two inhibitory amino acid neurotransmitters act via different mechanisms in the adrenal medulla. The results for glycine activity in adrenal medulla chromaffin cells are remarkably similar to those seen in CNS neuronal cells, and thus support the use of chromaffin cells as a model system for studying the mechanism of action of glycine in the central nervous system.