GTPase activity in mouse hippocampus membranes following prenatal exposure to heroin and phenobarbital.
Low Km 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 Km GTPase activities after prenatal exposure to phenobarbital exhibited a statistically significant (P < 0.05) decrease both in Km and Vmax values. Basal Vmax values were reduced from 152 +/- 10 in controls to 112 +/- 13 (pmol/mg protein/min, mean +/- SEM) in exposed mice. The Km values in the offspring of mice treated with phenobarbital were reduced from 1.55 +/- 0.21 to 0.96 +/- 0.11 (microM, mean +/- SEM); Vmax and Km 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 Vmax and Km values. It is postulated that these changes in G alpha protein activity may be related to the teratogenic effect of these drugs.
Zamir
I
I
Melvin A. and Eleanor Ross Laboratory for Studies in Neural Defects, Department of Anatomy and Embryology, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Yanai
J
J
D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects / Q000201:enzymology; D004789:Enzyme Activation; D005260:Female; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D006160:Guanosine Triphosphate / Q000378:metabolism; D003932:Heroin / Q000633:toxicity*; D006624:Hippocampus / Q000187:drug effects* / Q000196:embryology / Q000201:enzymology; D006868:Hydrolysis; D051379:Mice; D010634:Phenobarbital / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects
D003932:Heroin; D006160:Guanosine Triphosphate; D002217:Carbachol; D020558:GTP Phosphohydrolases; D010634:Phenobarbital