Abstract
The plasma membrane-bound enzyme, adenylate cyclase, serves as a signal transduction system for a wide variety of hormones and neurotransmitters, acting as extracellular messengers in the process of intercellular communication. This signal-generating role of the adenylate cyclase is clearly established for those hormones and neurotransmitters which after interaction with their specific receptors cause an increase in enzyme activity with subsequent increased levels of cyclic AMP acting as the intracellular second messenger (Robinson et al., 1971). Numerous studies on the mechanisms and components involved in the hormone-induced increase in cyclic AMP formation lead to the generally accepted concept that the complete system is composed of at least three distinct subunits, namely the hormone receptor acting as signal discriminator, the catalytic subunit catalyzing the formation of cyclic AMP from ATP, and a guanine nucleotide-binding regulatory component serving as coupler between the hormone-activated receptor and the catalyst (Ross & Gilman, 1980). On the other hand,
Present address: Psychiatrische Klinik der Universität Mainz, D-6500 Mainz, FRG.
Present address: Pharmakologisches Institut der Freien Universitat Berlin, D-1000 Berlin, FRG.
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References
AKTORIES, K., HUNGERER, K.D. , ROBBEL, L. & JAKOBS, K.H. (1984b). In Abstracts, Proc. 9th Int. Congr. Pharmac. London 1984, Basingstoke: Macmillan.
AKTORIES, K., SCHULTZ, G. & JAKOBS, K.H. (1982). Cholera toxin inhibits prostaglandin Ei but not adrenaline-induced stimulation of GTP hydrolysis in human platelet membranes. FEBS Lett., 146, 65–68.
AKTORIES, K., SCHULTZ, G. & JAKOBS, K.H. (1983). Adenylate cyclase inhibition and GTPase stimulation by somatostatin in S49 lymphoma cyc- variants are prevented by islet-activating protein. FEBS Lett., 158, 169–173.
AKTORIES, K. SCHULTZ, G. & JAKOBS, K.H. (1984a). In Neurotransmitter Receptors: Mechanisms of Action and Regulation, Kitto, S. (ed), New York: Plenum Press (in press).
BOKOCH, G.M., KATADA, T., NORTHUP, J.K., UI, M. & GILMAN, A.G. (1984). Purification and properties of the inhibitory guanine nucleotide-binding regulatory component of adenylate cylase. J. biol. Chem., 259, 3560–3567.
BRANDT, D.R., ASANO, T., PEDERSEN, S.E. & ROSS, E.M. (1983). Reconstitution of catecholamine-stimulated guanosinetriphosphatase activity. Biochemisty, 22, 4357–4362.
CASSEL, D. & PFEUFFER, T. (1978). Mechanism of cholera toxin action: Covalent modification of the guanyl nucleotide-binding protein of the adenylate cyclase system. Proc. natn. Acad. Sci. U.S.A., 75, 2669–2673.
CASSEL, D. & SELINGER, Z. (1977). Mechanism of adenylate cyclase activation by cholera toxin: Inhibition of GTP hydrolysis at the regulatory site. Proc. natn. Acad. Sci. U.S.A., 74, 3307–3311.
CASSEL, D. & SELINGER, Z. (1978). Mechanism of adenylate cyclase activation through the β-adrenergic receptor: Catecholamine-induced displacement of bound GDP by GTP. Proc. natn. Acad. Sci. U.S.A., 75, 4155–4159.
CODINA, J., HILDEBRANDT, J., IYENGAR, R., BIRNBAUMER, L., SEKURA, R.D. & MANCLARK, C.R. (1983). Pertussis toxin substrate, the putative Ni component of adenylyl cyclases, is an αβ heterodimer regulated by guanine nucleotide and magnesium. Proc. natn. Acad. Sci. U.S.A., 80, 4276–4280.
COOPER, D.M.F. (1982). Biomodal regulation of adenylate cyclase. FEBS Lett., 138, 157–163.
HILDEBRANDT, J.D., CODINA, J., RISINGER, R. & BIRNBAUMER, L. (1984). Identification of a γ subunit associated with the adenylyl cyclase regulatory proteins Ns and Ni J. biol. Chem., 259, 2039–2042.
HOFFMAN, B.B. & LEFKOWITZ, R.J. (1980). Radioligand studies of adrenergic receptors: New insights into molecular and physiological regulation. Ann. Rev. Pharmac. Toxic., 20, 581–608.
JAKOBS, K.H. (1983). Determination of the turn-off reaction for the epinephrine-inhibited human platelet adenylate cyclase. Eur. J. Biochem., 132, 125–130.
JAKOBS. K.H., AKTORIES, K., MINUTH, M. & SCHULTZ, G. (1984d). Inhibition of adenylate cyclase. Adv. Cyclic Nucleotide Res. (in press).
JAKOBS, K.H., AKTORIES, K. & SCHULTZ, G. (1981). Inhibition of adenylate cyclase by hormones and neurotransmitters. Adv. Cyclic Nucleotide Res., 14, 173–187.
JAKOBS, K.H., AKTORIES, K. & SCHULTZ, G. (1984a). Mechanism of pertussis toxin action on the adenylate cyclase system. Inhibition of the turn-on reaction of the inhibitory regulatory site. Eur. J. Biochem., 140, 177–181.
JAKOBS, K.H., AKTORIES, K. & SCHULTZ, G. (1984b). Mechanisms and components involved in adenylate cyclase inhibiton by hormones. Adv. Cyclic Nucleotide Res., 17, 135–143.
JAKOBS, K.H., GEHRING, U., GAUGLER, B., PFEUFFER, T. & SCHULTZ, G. (1983a). Occurrence of an inhibitory guanine nucleotide-binding regulatory component of the adenylate cyclase system in cyc- variants of S49 lymphoma cells. Eur. J. Biochem., 130, 605–611.
JAKOBS, K.H., MINUTH, M. & AKTORIES, K. (1984c). Sodium regulation of hormone-sensitive adenylate cyclase. J. Rec. Res. (in press).
JAKOBS, K.H., SAUR, W. & SCHULTZ, G. (1978). Inhibition of platelet adenylate cyclase by epinephrine requires GTP. FEBS Lett., 85, 167–170.
JAKOBS, K.H. & SCHULTZ, G. (1983). Occurrence of a hormone-sensitive inhibitory coupling component of the adenylate cyclase in S49 lymphoma cyc- variants. Proc. natn. Acad. Sci. U.S.A., 80, 3899–3902.
JAKOBS, K.H., SCHULTZ, G., GAUGLER, B. & PFEUFFER, T. (1983b). Inhibition of Ns-protein-stimulated human platelet adenylate cyclase by epinephrine and stable GTP analogs. Eur. J. Biochem., 134, 351–354.
KATADA, T., NORTHUP, J.K., BOKOCH, G.M., UI, M. & GILMAN, A.G. (1984). The inhibitory guanine nucleotide-binding regulatory component of adenylate cyclase. Subunit dissociation and guanine nucleotide-dependent hormonal inhibition. J. biol. Chem., 259, 3578–3585.
KATADA, T. & UI, M. (1982). Direct modification of the membrane adenylate cyclase system by isletactivating protein due to ADP-ribosylation of a membrane protein. Proc. natn. Acad. Sci. U.S.A., 79, 3129–3133.
LIMBIRD, L.E. & SPECK, J.K. (1983). N-Ethylmaleimide, elevated temperature, and digitonin solubilization eliminate guanine nucleotide but not sodium effects on human platelet α2-adrenergic receptor-agonist interactions. J. Cyclic Nucleotide Prot. Phosphor., 9, 191–201.
MANNING, D.R. & GILMAN, A.G. (1983). The regulatory components of adenylate cyclase and transducin. A family of structurally homologous guanine nucleotide-binding proteins. J. biol. Chem., 258, 7059–7063.
MURAYAMA, T. & UI, M. (1983). Loss of the inhibitory function of the guanine nucleotide regulatory component of adenylate cyclase due to its ADP ribosylation by islet-activating protein, pertussis toxin, in adipocyte membranes. J. biol. Chem., 258, 3319–3326.
MURAYAMA, T. & UI, M. (1984). [3H]GDP release from rat and hamster adipocyte membranes independently linked to receptors involved in activation or inhibition of adenylate cyclase. Differential susceptibility to two bacterial toxins. J. biol. Chem., 259, 761–769.
NORTHUP, J.K., STERNWEISS, P.C., SMIGEL, M.D., SCHLEIFER, L.S., ROSS, E.M. & GILMAN, A.G. (1980). Purification of the regulatory component of adenylate cyclase. Proc. natn. Acad. Sci. U.S.A., 77, 6816–6520.
PFEUFFER, T. (1977). GTP-binding proteins in membranes and the control of adenylate cyclase activity. J. biol. Chem., 252, 7224–7234.
ROBINSON, G.A., BUTCHER, R.W. & SUTHERLAND, E.W. (1971). Cyclic AMP, New York: Academic Press.
RODBELL, M., BIRNBAUMER, L., POHL, S.L. & KRANS, H.M. (1971). The glucagon-sensitive adenyl cyclase system in plasma membranes of rat liver. V. An obligatory role of guanyl nucleotides in glucagon action. J. biol. Chem., 246, 1877–1882.
ROSS, E.M. & GILMAN, A.G. (1980). Biochemical properties of hormone-sensitive adenylate cyclase. A. Rev. Biochem., 49, 533–564.
SEAMON, K.B. & DALY, J.W. (1981). Forskolin: a unique diterpene activator of cyclic AMP generating systems. J. Cyclic Nucleotide Res., 7, 201–224.
SMIGEL, M. KATADA, T., NORTHUP, J.K., BOKOCH, G.M., UI, M. & GILMAN, A.G. (1984). Mechanisms of guanine nucleotide-mediated regulation of adenylate cyclase activity. Adv. Cyclic Nucleotide Res., 17, 1–19.
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Jakobs, K.H., Aktories, K., Minuth, M., Schultz, G. (1984). Inhibitory modulation of adenylate cyclase. In: Paton, W., Mitchell, J., Turner, P. (eds) IUPHAR 9th International Congress of Pharmacology London 1984. Palgrave Macmillan, London. https://doi.org/10.1007/978-1-349-17613-7_29
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