GTPase activity in mouse hippocampus membranes following prenatal exposure to heroin and phenobarbital

Low K_m high affinity GTPase activity, with and without muscarinic receptor stimulation with 1 mM carbachol, was measured in membrane preparations of mouse hippocampus prenatally exposed to phenobarbital or heroin. Basal and carbachol-stimulated low K_m GTPase activities after prenatal exposure to phenobarbital exhibited a statistically significant (P < 0.05) decrease both in K_m and V_max values. Basal V_max values were reduced from 152 ± 10 in controls to 112 ± 13 (pmol/mg protein/min, mean ± SEM) in exposed mice. The K_m values in the offspring of mice treated with phenobarbital were reduced from 1.55 ± 0.21 to 0.96 ± 0.11 (μM, mean ± SEM); V_max and K_m values after carbachol stimulation were similarly affected. Prenatal exposure to heroin did not change the GTPase activities, basal or carbachol-stimulated, with only a non-significant increase in both V_max and K_m values. It is postulated that these changes in Gα protein activity may be related to the teratogenic effect of these drugs.