Differential effects of cytosolic modulators of fluoride-stimulated adenylate cyclase activity in striatum and cerebral cortex

Abstract

The effects of sodium fluoride (NaF) and ethanol on adenylate cyclase activity were investigated in mouse and rat striatum and cerebral cortex. In a crude homogenate of striatum, NaF (10 mM) had no effect on adenylate cyclase activity even though guanyl-5'-yl-imidodiphosphate (GppNHp) increased enzyme activity by two-fold. Addition of 300 mM ethanol increased basal and GppNHp-stimulated activity and allowed expression of an effect of NaF. Stimulation of adenylate cyclase activity by NaF was also observed after sedimentation and resuspension of membranes. Readdition of the supernatant to washed membranes caused a decrease in maximal NaF-stimulated activity without any change in the concentration of NaF required for half-maximal stimulation. The inhibitory effect of the supernatant was resistant to heat but was eliminated by the addition of ethanol or perchloric acid. Inhibition of NaF-stimulated adenylate cyclase activity in striatal tissue was also observed when assays were carried out in the presence of a 20,000 X g supernatant prepared from cerebral cortex. NaF-stimulated activity in cortical tissue was, on the other hand, enhanced in the presence of a 20,000 X g supernatant prepared from either cortex or striatum. This suggests that there is a basic difference between the adenylate cyclase systems of these tissues.