Impairment of adenylyl cyclase signal transduction in mecobalamin-deficient rats

Abstract

This study examined alterations in the β-adrenoceptor-G_s-adenylyl cyclase system in cerebral cortex membranes from vitamin B₁₂-deficient rats fed a diet lacking vitamin B₁₂ (mecobalamin) for 15 weeks. Basal, 5'-guanylylimidodiphosphate (GppNHp)-, isoproterenol-, and forskolin-stimulated adenylyl cyclase activities were significantly reduced in mecobalamin-deficient rats compared with those in control rats. However, no significant differences were observed in the amount and function of G_s, estimated by immunoblotting and guanine nucleotide photoaffinity labeling, respectively, or in the densities and the dissociation constants of β-adrenoceptors, estimated by [¹²⁵I] pindolol binding, between control and the deficient rats. These results indicate that vitamin B₁₂ deficiency results in the impairment of the coupling among the β-adrenoceptor, G_s, and the catalytic subunit of adenylyl cyclase, and in dysfunction of the catalytic subunit of the enzyme, suggesting that vitamin B₁₂ participates in the regulation of neuronal adenylyl cyclase signal transduction.