Effect of Ca(2+)-channel blockers, Ca(2+)-ionophore and increased pyrene excimer formation on the microsomal glucose-6-phosphatase.

The dependence of microsomal glucose-6-phosphatase (G-6-Pase) activity on Ca2+ as well as the membrane lipid microviscosity was studied by the effect of Ca(2+)-channel blockers (namely verapamil and nifedipine), Ca(2+)-ionophore, A23187 and pyrene excimer formation. Channel blockers depressed the G-6-Pase and Ca(2+)-ATPase while the ionophore increased these activities. Dimethyl sulfoxide, a known membrane surface active agent showed no change. Ca(2+)-uptake into the membrane has expectedly been lowered by the channel blockers while the ionophores facilitated the ion flux. Excimer formation of the fluorescent probe, pyrene as an indicator of increased membrane fluidity, and microviscosity calculated from there on, showed that Ca(2+)- and lipid microenvironment in the membrane significantly influenced the activity of G-6-Pase. Membrane lipid composition such as phospholipid/cholesterol molar ratio which also indicates an increased membrane fluidity is markedly increased with the ionophore but decreased with the channel blockers, while protein/phospholipid ratio remained unchanged. Microsomal G-6-Pase is a multicomponent multifunctional protein. It is argued that Ca2+ may play the role of an obligatory cofactor not only for the hydrolysis of G-6-P (catalytic part of the enzyme) but also involved in the regulation of substrate and product transport in or out of the endoplasmic reticulum lumen.

Efecto de la aspirina, cafeina y diazepam sobre la actividad de la glucosa 6 fosfatasa, succinico deshidrogenasa y beta galactosidasa acida en la placenta humana / Effect os aspirin, caffeine and diazepam on glucose 6-phosphatase, succinic dehydrogenase, and acid-galactosidase in human placenta

Se estudio "in vitro" la actividad enzimatica de la beta galactosidasa acida, glucosa 6 fosfatasa y succinico deshidrogenasa para determinar si se afectaban en presencia de aspirina, cafeina y diazepam en homogeneizado total de placenta humana. Se utilizaron dosis de 10, 50 y 100 /ml de cada farmaco, y se determino si existia diferencia significativa en ausencia de los farmacos y en presencia de los mismos mediante la prueba t de Student para series apareadas. En todas las concentraciones de los tres farmacos la beta galactosidasa acida presento un aumento altamente significativo. La glucosa 6 fosfatasa y la succinico deshidrogenasa tuvieron una disminucion altamente significativa, aunque en esta ultima la disminucion fue solosignificativa con la dosis mas pequena. Se concluye que la presencia de aspirina, cafeina y diazepam produce alteraciones en la actividad de las enzimas estudiadas que pueden provocar trastornos del metabolismo placentario