Modulation of guanosine triphosphatase activity of G proteins by arachidonic acid in rat Leydig cell membranes. Endocrinology 141:1093–1099

Previous results from our group have indicated that arachidonic acid decrease cAMP production through a modification of heterotri-meric G proteins. In the present study, we have characterized the high affinity GTPase activity present in Leydig cell membranes and its regulation by fatty acids. The high-affinity GTPase activity, mea-sured as [g32P] GTP hydrolysis rate, was both time and protein con-centration dependent. Arachidonic acid elicited a dose-dependent in-hibition of enzyme activity with an IC50 5 26.7 6 1.1 mM. The existence of only two double bonds in linoleic acid is reflected by a decrease in its inhibitory activity (IC50 5 34 6 2.3 mM). Saturated fatty acids showed no effect at this level. The kinetic analysis as interpreted by Lineweaver-Burk plots, indicated that 50 mM arachidonic acid had no effect on the apparent affinity for GTP, but resulted in a 40% decreases in the maximal velocity of the reaction. Arachidonic aci