PARTICIPATION OF TUBULIN IN THE STIMULATORY REGULATION OF ADENYLYL-CYCLASE IN RAT CEREBRAL-CORTEX MEMBRANES

This study examined effects of tubulin on the activation of adenylyl c yclase in rat cerebral cortex membranes. Tubulin, prepared from rat br ain by polymerization with the hydrolysis-resistant GTP analogue 5'-gu anylylimidodiphosphate (GppNHp) caused significant activation of the e nzyme by similar to 156% under conditions in which stimulation rather than inhibition of the enzyme was favored. Tubulin-GppNHp activated is oproterenol-sensitive adenylyl cyclase, potentiated forskolin-stimulat ed activity of the enzyme, and reduced agonist binding affinity for P- adrenergic receptors. When tubulin, polymerized with the hydrolysis-re sistant photoaffinity GTP analogue [P-32]P-3(4-azidoanilido)-P-1-5'-GT P ([P-32]AAGTP), was incubated with cerebral cortex membranes, AAGTP w as transferred from tubulin to G(s alpha) as well as G(i alpha). These results suggest that, in rat cerebral cortex membranes, the tubulin d imer participates in the stimulatory regulation of adenylyl cyclase by transferring guanine nucleotide to G(s alpha) as well as affecting th e Gi-mediated inhibitory pathway.