Ontogeny of calmodulin and calmodulin-dependent adenylate cyclase in rat brain

The development of calmodulin, calmodulin-dependent adenylate cyclase and beta-adrenergic receptors was studied in the rat brain. Membrane-bound calmodulin detected was approximately 40-50% of the total calmodulin throughout the postnatal development of either in the cerebrum or cerebellum. No significant difference was found between the quantitative patterns of the membrane-bound and cytosolic calmodulin during the entire period of postnatal development in either of these tissues. Both the cytosolic and membrane-bound calmodulin were present in low concentrations in the immature brain after birth. Their contents rapidly increased during the second postnatal week. Subsequently, the cytosolic calmodulin content remained constant, but showed a considerable decrease in the particulate fraction after day 14. Basal adenylate cyclase activity in the rat cerebrum slowly increased up to the second postnatal week and decreased after day 14. The responsiveness to calmodulin of this enzyme remained unaltered during postnatal development, whereas fluoride and guanine nucleotide sensitivities increased in the same period. The maximum number of (-)-[3H]dihydroalprenolol binding site sharply increased during day 9-14 in the rat cerebrum, although the dissociation constant Kd of the binding site was not affected by age. The results in the latter study suggest that calmodulin-dependent adenylate cyclase may be already present in the earlier postnatal ages of the rat brain, while the beta-adrenergic receptor and guanine nucleotide regulatory unit, both of which are required for a hormone-sensitive adenylate cyclase, may sharply increase in the second postnatal week.