Summary
-
1.
Ca2+ and cAMP both act as intracellular second messengers of receptor activation. In neuronal tissue, Ca2+ acting via calmodulin can elevate cAMP levels. This regulation by Ca2+ provides a means whereby the elevation of intracellular [Ca2+] might modulate cAMP generation.
-
2.
In the present studies, the impact of the Ca2+/calmodulin regulation on receptor-mediated stimulation of activity is compared in striatum and hippocampus—regions of differing sensitivity to Ca2+/camodulin. Ca2+/calmodulin stimulated striatal and hippocampal adenylate cyclase activity by 1.4-and 2.7-fold respectively, while dopamine and vasoactive intestinal peptide (VIP) stimulated the enzyme activity of these respective regions by 1.3- and 2-fold.
-
3.
In the presence of Ca2+/calmodulin, the dopamine dose-response curve in the striatum was shifted upward, without alteration of the slope of the curve or of the maximal stimulation of activity elicited by dopamine. In the hippocampus, the ability of VIP to stimulate adenylate cyclase activity was reduced by the presence of calmodulin.
-
4.
The dose dependence of these actions of calmodulin was examined. In the striatum, the stimulation of adenylate cyclase activity by 0.1 to 0.3µM calmodulin obscured dopamine stimulation, while 1 to 10µM was additive with the dopamine stimulation. In the hippocampus, all concentrations of calmodulin (0.1 to 10µM) reduced VIP-mediated stimulation of enzyme activity.
-
5.
These data suggest that the ratio of calmodulin-sensitive to calmodulin-insensitive adenylate cyclase activity varies in different rat brain regions and that, in those regions in which this ratio is low (e.g., rat striatum and most peripheral systems), calmodulin- and receptor-mediated activation of adenylate cyclase activity will be additive, while in those systems in which this ratio is high (e.g., most of the central nervous system), calmodulin will reduce receptor-mediated stimulation of enzyme activity.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Ahlijanian, M. K., and Cooper, D. M. F. (1987). Calmodulin may play a pivotal role in neurotransmitter-mediated inhibition and stimulation of rat cerebellar adenylate cyclase.Mol. Pharmacol. 32127–132.
Ahlijanian, M. K., Halford, M. K., and Cooper, D. M. F. (1987). Ca2+/calmodulin distinguishes between guanyl-5′-yl-imidodiphosphate- and opiate-mediated inhibition of rat striatal adenylate cyclase.J. Neurochem. 491308–1314.
Brostrom, C. O., Huang, Y. C., Breckenridge, B. M., and Wolff, D. J. (1975). Identification of a calcium-binding protein as a calcium-dependent regulator of brain adenylate cyclase.Proc. Natl. Acad. Sci. USA 7264–68.
Brostrom, M. A., Brostrom, C. O., Breckenridge, B. M., and Wolff, D. J. (1976). Regulation of adenylate cyclase from Glial tumor cells by calcium and a calcium-binding protein.J. Biol. Chem. 2514744–4750.
Cheung, W. Y., Bradham, L. E., Lynch, T. J., Lin, Y. M., and Tallant, E. A. (1975). Protein activator of cyclic 3′:5′-nucleotide phosphodiesterase of bovine or rat brain also activates its adenylate cyclase.Biochem. Biophys. Res. Commun. 661055–1062.
Cooper, D. M. F., Bier-Laning, C. M., Halford, M. K., Ahlijanian, M. K., and Zahniser, N. R. (1986). Dopamine, acting through D-2 receptors, inhibits rat striatal adenylate cyclase by a GTP-dependent process.Mol. Pharmacol. 29113–119.
Gilman, A. G. (1987). G proteins: Transducers of receptor-generated signals.Annu. Rev. Biochem. 56615–649.
Girardot, J. M., Kempf, J., and Cooper, D. M. F. (1983). Role of calmodulin in the effect of guanyl nucleotides on rat hippocampal adenylate cyclase: Involvement of adenosine and opiates.J. Neurochem. 41848–859.
Gnegy, M., and Treisman, G. J. (1981). Effect of calmodulin on dopamine-sensitive adenylate cyclase activity in rat striatal membranes.Mol. Pharmacol. 19256–263.
Gnegy, M. E., Uzunov, P., and Costa, E. (1976). Regulation of dopamine stimulation of striatal adenylate cyclase by an endogenous Ca2+-binding protein.Proc. Natl. Acad. Sci. USA 733887–3890.
Hoskins, B., Burton, C. K., Liu, D. D., Porter, A. B., and Ho, I.K. (1986). Regional and subcellular calmodulin content of rat brain.J. Neurochem. 46303–304.
Klee, C. B., Crouch, T. H., and Richman, P. G. (1980). Calmodulin.Annu. Rev. Biochem. 49489–515.
Lowry, O. H., Rosebrough, N. J., Farr, A. L., and Randall, R. J. (1951) Protein measurement with the Folin phenol reagent.J. Biol. Chem. 193265–275.
Malnoe, A. E., Stein, A., and Cox, J. A. (1983). Synergistic activation of bovine cerebellum adenylate cyclase by calmodulin andβ-adrenergic agonists.Neurochem. Int. 565–72.
Malnoe, A. E., Stein, A., and Cox, J. A. (1983). Synergistic activation of bovine cerebellum adenylate cyclase by calmodulin andβ-adrenergic agonists.Neurochem. Int. 565–72.
Perez-Reyes, E., and Cooper, D. M. F. (1987). Calmodulin stimulation of the rat cerebral cortical adenylate cyclase is required for the detection of guanine nucleotide- or hormone-mediated inhibition.Mol. Pharmacol. 32212–216.
Rosenberg, G. B., and Storm, D. R. (1987). Immunological distinction between calmodulin-sensitive and calmodulin-insensitive adenylate cyclase.J. Biol. Chem. 2627623–7628.
Salomon, Y., Londos, C., and Rodbell, M. (1974). A highly sensitive adenylate cyclase assay.Anal. Biochem. 58541–548.
Yeager, R. E., Heideman, W., Rosenberg, G. B., and Storm, D. R. (1985). Purification of the calmodulin sensitive adenylate cyclase from bovine cerebral cortex.Biochemistry 243776–3783.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Ahlijanian, M.K., Cooper, D.M.F. Distinct interactions between Ca2+/calmodulin and neurotransmitter stimulation of adenylate cyclase in striatum and hippocampus. Cell Mol Neurobiol 8, 459–469 (1988). https://doi.org/10.1007/BF00711229
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00711229