Guanine nucleotides have a direct inhibitory effect on polyphosphoinositide turnover in rat cortical synaptosomes

Abstract

1. 1. The possible involvement of guanosine 5'-triphosphate (GTP)-binding proteins in the receptor mediated polyphosphoinositide (PPI) turnover event was investigated in rat cortical synaptosomes. 2. 2. It was studied under the effects of guanine nucleotides on 32P i incorporation into synaptosomal phospholipids in the absence or presence of carbachol. 3. 3. The basal 32P i incorporation into these phospholipids was altered by the presence of 1 mM carbachol: i.e. a decrease in 32P i incorporation into phosphatidylinositol-4,5-bisphosphate and phosphatidylinositol-4-phosphate and an increase in the incorporation of 32P i into phosphatidylinositol and phosphatidic acid. 4. 4. In the presence of guanine nucleotides: GTP, Gpp(NH)p and GDP at suitable concentrations, there was a general decreasing effect on 32P i incorporation into all 4 phospholipids, which are all involved in PPI turnover cycle, either in the basal or carbachol-stimulated levels. 5. 5. There was no selective effect among the guanine nucleotides studied on this PPI turnover event. It is, therefore, likely that these nucleotides have a direct inhibitory effect on PPI turnover, and this action may not act through a GTP-binding protein.