Central receptor binding and cardiovascular effects of GABA analogues in the cat

Abstract

1. 1. Several structural analogues of GABA were shown to be inhibitors of GABA A receptor binding in membranes from cat cerebral cortex. 2. 2. These compounds were 3-aminopropanesulfonic acid (APS; IC 50 = 0.04 μM), imidazoleacetic acid (IMA; IC 50 = 0.4 μM), morpholinopropanesulfonic acid (MOPS; IC 50 = 1.6 μM), 5-phenylpyrrolepropionic acid (PPP; IC 50 = 15 μM), aminoethanethiosulfonic acid (AETS; IC 50 = 22 μM), 3-amino-3-phenylpropionic acid (APP; IC 50 = 35 μM), meta-aminobenzoic acid (MABA; IC 50 = 58 μM) and urocanic acid (UCA; IC 50 = 354 μM). The IC 50 value for GABA was 0.03 μM. 3. 3. GABA, PPP, AETS, MABA and UCA were previously shown to reduce arterial pressure in the cat after intracerebroventricular infusion. 4. 4. In the present study MOPS (ED 50 = 0.26 nmol/kg), APS (ED 50 = 4.7 nmol/kg), APP (ED 50 = 49 nmol/kg), and IMA (ED 50 = 350 nmol/kg) were also found to be able to decrease blood pressure when infused into the fourth ventricle. 5. 5. All nine compounds reduced blood pressure to the same extent, but in some cases their relative potencies (ED 50 values) exhibited significant differences. 6. 6. When the IC 50 values for receptor binding were plotted against the ED 50 values for the cardiovascular effects, no significant correlation emerged. 7. 7. This lack of a correlation does not necessarily imply that the reductions in blood pressure elicited by the drugs are not related to an activation of central GABA A receptors. 8. 8. Instead, it highlights the difficulties that are sometimes encountered in attempting to obtain quantitative measurements after intracerebroventricular infusion.