title: Impairment of adenylyl cyclase signal transduction in mecobalamin-deficient rats.
abstract: This study examined alterations in the beta-adrenoceptor-G5-adenylyl cyclase system in cerebral cortex membranes from vitamin B12-deficient rats fed a diet lacking vitamin B12 (mecobalamin) for 15 weeks. Basal, 5(7)-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 G5- estimated by immunoblotting and guanine nucleotide photoaffinity labeling, respectively, or in the densities and the dissociation constants of beta-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 beta-adrenoceptor, G5- 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.
authors.affiliation: Department of Pharmacology, School of Medicine, Sapporo Medical University, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Hatta
authors.forename: M
authors.initials: M
authors.lastname: Watanabe
authors.forename: H
authors.initials: H
authors.lastname: Ikeda
authors.forename: H
authors.initials: H
authors.lastname: Kamada
authors.forename: T
authors.initials: T
authors.lastname: Saito
authors.forename: H
authors.initials: H
authors.lastname: Ohshika
mesh_terms: D000067956:Adenylyl Cyclase Inhibitors; D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism*; D005576:Colforsin / Q000037:antagonists & inhibitors; D019204:GTP-Binding Proteins / Q000032:analysis*; D006165:Guanylyl Imidodiphosphate / Q000037:antagonists & inhibitors; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000037:antagonists & inhibitors; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000032:analysis; D015398:Signal Transduction / Q000502:physiology*; D014805:Vitamin B 12 / Q000031:analogs & derivatives* / Q000032:analysis
chemical_list: D000067956:Adenylyl Cyclase Inhibitors; D011943:Receptors, Adrenergic, beta; D005576:Colforsin; D006165:Guanylyl Imidodiphosphate; C019476:mecobalamin; D019204:GTP-Binding Proteins; D007545:Isoproterenol; D014805:Vitamin B 12