Summary
We have measured the effects of the carboxylic Ca++ ionophore A23187 on muscle tension, resting potential and 3-O-methylglucose efflux. The ionophore produces an increase in tension that is dependent on external Ca++ concentration since (a) the contracture was blocked by removing external Ca++ and (b) its size was increased by raising outside Ca++. Neither resting potential nor resting and insulin-stimulated sugar efflux were modified by the ionophore. These data imply that the action of insulin is not mediated by increasing cytoplasmic [Ca++]. Additional support for this conclusion was obtained by testing the effects of caffeine on sugar efflux. This agent, which releases Ca++ from the reticulum, did not increase resting sugar efflux and inhibited the insulin-stimulated efflux. Incubation in solutions containing butyrated derivatives of cyclic AMP or cyclic GMP plus theophylline did not modify the effects of insulin on sugar efflux. Evidence suggesting that our experimental conditions increased the cytoplasmic cyclic AMP activity was obtained.
Similar content being viewed by others
References
Armstrong, C.M., Bezanilla, F.M., Horowicz, P. 1972. Twitches in the presence of ethylene glycol bis (β-aminoethyl ether)-N′,N′-tetraecetil acid.Biochim. Biophys. Acta 267:605
Ball, E.G., Jungas, R.L. 1964. Some effects of hormones on the metabolism of adipose tissue.Recent Prog. in Horm. Res. 20:183
Bonting, S.L., Simon, K.A., Hawkins, N.M. 1961. Studies on sodium-potassium activated adenosine triphosphatase.Arch. Biochem. Biophys. 95:416
Case, G.D., VanderKooi, J.M., Scarpa, A. 1974. Physical properties of biological membranes determined by the fluorescence of the calcium ionophore A23187.Arch. Biochem. Biophys. 162:174
Chambaut, A., Eboué-Bonis, D., Hanoune, J., Clauser, H. 1969. Antagonistic action between dibutyryl adenosine-3′–5′-cyclic monophosphate and insulin on the metabolism of the surviving rat diaphragm.Biochem. Biophys. Res. Commun. 34:283
Clausen, T., Elbrink, J., Dahl-Hansen, A.B. 1975. The relationship between the transport of glucose and cations across cell membranes in isolated tissues. IX. The role of cellular calcium in the activation of the glucose transport system in rat soleus muscle.Biochem. Biophys. Acta 375:292
Danforth, W.H., Helmereich, E., Cori, C. 1962. The effect of contraction and of epinephrine on the phosphorylase activity of frog sartorius muscle.Proc. Nat. Acad. Sci. 48:1191
Devore, D.I., Nastuk, W.L. 1975. Effects of „calcium ionophore” X537A on frog muscle.Nature (London) 253:644
Elbrink, J., Bihler, I. 1975. Membrane transport; its relation to cellular metabolic rates.Science 188:1177
Exton, J.H., Lewis, S.N., Ho, R.J., Robison, G.A., Park, C.R. 1971. The role of cyclic AMP in the interaction of glucagon and insulin in the control of liver metabolism.Ann. N. Y. Acad. Sci. 185:85
Goldberg, N., Villar-Palasi, C., Sasko, H., Larner, J. 1967. Effects of insulin treatment on muscle 3′5′ cyclic adenylate levelsin vivo andin vitro.Biochim. Biophys. Acta 148:665
Gourley, D.R.H. 1965. Effects of insulin on potassium exchange in normal and ouabaintreated skeletal muscle.J. Pharmacol. Exp. Ther. 148:339
Grinstein, S., Erlij, D. 1974. Unmasking of latent sodium pump sites in frog muscle by insulin.Nature (London) 251:57
Hainaut, K., Desmedt, J.E. 1974. Calcium ionophore A23187 potentiates twitch and intracellular Ca++ release in single muscle fibres.Nature (London) 252:407
Harris, E.J. 1963. Distribution and movement of muscle chloride.J. Physiol. (London) 166:87
Hellam, D.C., Podolsky, R.J. 1968. Force measurements in skinned muscle fibres.J. Physiol. (London) 200:807
Hollenberg, M.D., Cuatrecasas, P. 1975. Insulin: interaction with membrane receptors and relationship to cyclic purine nucleotides and cell growth.Fed. Proc. 34:1556
Holloszy, J.O., Narahara, H.T. 1967. Enhanced permeability to sugar associated with muscle contraction. Studies of the role of Ca++.J. Gen. Physiol. 50:551
Illiano, G., Tell, G.P.E., Siegel, M.I., Cuatrecasas, P. 1973. Guanosine 3′∶5′ cyclic monophosphate and the action of insulin and acetylcholine.Proc. Nat. Acad. Sci. USA 70:2443
Kaukel, E., Mudhenk, K., Hinz, H. 1972. N6 Monobutyryladenosine 3′∶5′ monophosphate in Hela as the biologically active derivative of dibutyryladenosine 3′∶5′ monophosphate 53 cells.Eur. J. Biochem. 27:197
Keely, S.L., Corbin, J.D., Park, C.R. 1975. Regulation of adenosine 3′–5′ monophosphate dependent protein kinase regulation of the heart enzyme by epinephrine, glucagon, insulin and 1-methyl-3-isobutylxanthine.J. Biol. Chem. 250:4832
Kipnis, D.M., Noall, M.W. 1958. Stimulation of aminoacid transport by insulin in the isolated rat diaphragm.Biochim. Biophys. Acta 28:226
Kissebah, A.H., Hope-Gill, H., Vydelingum, N., Tullock, B.R., Clarke, P.V., Fraser, T.R. 1975. Model of insulin action.Lancet 7899:144
Kohn, P.G., Clausen, T. 1971. The relationship between the transport of glucose and cations across cell membranes in isolated tissues.Biochim. Biophys. Acta 225:277
Larner, J., Villar-Palasi, C., Goldberg, N.D., Bishop, J.S., Huijing, F., Wenger, J.I., Sasko, H., Brown, N.B. 1968. Hormonal and non-hormonal control of glycogen-synthesis.In: Control of glycogen Metabolism. W.J. Whelan, editor. P. 1. Academic Press, New York
Levine, R., Goldstein, M., Klein, S., Huddleston, B. 1949. The action of insulin on the distribution of galactose in eviscerated nephrectomized dogs.J. Biol. Chem. 179:985
Lostroh, A.J., Krahl, M.E. 1973. Insulin action: accumulation in vitro of Mg2+ and K+ in rat uterus: ion pump activity.Biochim. Biophys. Acta 291:260
McLaughlin, S., Eisenberg, M. 1975. Antibiotics and membrane biology.Annu. Rev. Biophys. Bioeng. 4:335
McAfee, D.A., Greengard, P. 1971. Adenosine 3′∶5′-monophosphate in nervous tissue increase associated with synaptic transmission.Science 171:1156
Narahara, H.T., Holloszy, J.O. 1974. The actions of insulin, trypsin, and electrical stimulation on amino acid transport in muscle.J. Biol. Chem. 249:5435
Neelon, F.A., Birch, B.M. 1973. Cyclic adenosine 3′∶5′ monophosphate-dependent protein kinase. Interaction with butyrylated analogues of cyclic adenosine 3′ 5′ monophosphate.J. Biol. Chem. 248:8361
Ong, S., Whitley, T., Stowe, N., Steiner, A.L. 1975. Immunohistochemical localization of 3′5 cAMP and 3′5′ cGMP in rat liver, intestine and testis.Proc. Nat. Acad. Sci. USA 72:2022
Pressman, B.C. 1972. Carboxylic ionophores as mobile carriers for divalent ions.In: The role of Membranes in Metabolic Regulation. M.A. Mehlman and R.W. Hanson, editors. Pp. 149–164. Academic Press, New York
Reed, P.W. 1972. A23187 A divalent cation ionophore.Fed. Proc. 31:432
Reed, P.W., Lardy, H.A. 1972. Antibiotic A23187 as a probe for the study of calcium and magnesium function in biological systems.In: the Role of Membranes in Metabolic Regulation. M.A. Mehlman and R.W. Hanson, editors. Pp. 111–131. Academic Press, New York
Stone, T.W., Taylor, D.A., Bloom, F.E. 1975. Cyclic AMP and cyclic GMP may mediate opposite neuronal responses in the rat cerebral cortex.Science 187:845
Swislocki, N.I. 1970. Decomposition of dibutyryl cyclic AMP in aqueous buffers.Anal. Biochem. 38:260
Triggle, C.R., Grant, W.F., Triggle, D.D.J. 1975. Intestinal smooth muscle contraction and the effects of cadmium and A23187.J. Pharmacol. Exp. Ther. 194:182
Weber, A., Herz, R. 1968. The relationship between contractures of intact muscle and the effect of caffeine on reticulum.J. Gen. Physiol. 52:750
Wool, I.G., Castles, J.J., Leader, D.P., Fox, A. 1972. Insulin and the functions of muscle ribosomes.In: Handbook of Physiology Section 7, Endocrinology; Vol. I, Endocrine Pancreas. pp. 385–394. American Physiological Society, Washington
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Grinstein, S., Erlij, D. Action of insulin and cell calcium: Effect of ionophore A23187. J. Membrain Biol. 29, 313–328 (1976). https://doi.org/10.1007/BF01868968
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF01868968