Abstract
The concept of adenosine receptors has been developed from several independent lines of research. A first biochemical basis for the study of the molecular mechanisms of adenosine action was discovered when Sattin and Rall [1] and Shimizu et al. [2] described the potent stimulatory effects of adenosine and adenine nucleotides on cyclic AMP formation in brain slices. These authors proposed the existence of an external adenosine receptor that stimulates adenylate cyclase in a hormone-like manner and that is competitively inhibited by several methylxanthines. In other tissues, adenosine was found to inhibit adenylate cyclase-dependent reactions [3–5]. Based on these observations, two types of adenosine receptors have been classified by the use of selected adenosine analogues [6]. The inhibitory adenosine receptor has a high affinity for adenosine and has been designated Ri. The stimulatory adenosine receptor has a lower affinity for adenosine and has been designated Ra. An alternative nomenclature, using Al for the inhibitory receptor and A2 for the stimulatory receptor, has been proposed [5]. Moreover, nearly all cyclases contain an additional inhibitory P site located at the internal side of the cell membrane [7].
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References
Sattin A, Rail TW: The effect of adenosine and adenine nucleotides on the cyclic adenosine 3′,5′-phosphate content of guinea pig cerebral cortex slices. Mol Pharmacal 6: 13–23, 1970.
Shimizu H, Creveling CR, Daly J: Stimulated formation of adenosine 3′,5′-cyclic phosphate in cerebral cortex: Synergism between electrical activity and biogenic amines. Proc Natl Acad Sci USA 65: 1033–1040, 1970.
Fain JN, Pointer RH, Ward WF: Effects of adenosine nucleosides on adenylate cyclase, phosphodiesterase, cyclic adenosine monophosphate accumulation, and lipolysis in fat cells. J Biol Chem 247: 6866–6872, 1972.
Schwabe U, Ebert R, Erbler HC: Adenosine release from isolated fat cells and its significance for the effects of hormones on cyclic 3′,5′-AMP levels and lipolysis. Naunyn Schmiedebergs Arch Pharmacal 276: 133–148, 1973.
Van Calker D, Müller M, Hamprecht B: Adenosine inhibits the accumulation of cyclic AMP in cultured brain cells. Nature 276: 839–841, 1978.
Londos C, Cooper DMF, Wolff J: Subclasses of external adenosine receptors. Proc Natl Acad Sci USA 77: 2551–2554, 1980.
Londos C, Wolff J: Two distinct adenosine-sensitive sites on adenylate cyclase. Proc Natl Acad Sci USA 74: 5482–5486, 1977.
Burnstock G: Past and current evidence for the purinergic nerve hypothesis, in Baer HP, Drummond GI (eds): Physiological and Regulatory Functions of Adenosine and Adenine Nucleotides. New York, Raven Press, 1979, pp 3–32.
Schütz W, Tuisl E: Evidence against adenylate cyclase-coupled adenosine receptors in the guinea pig heart. Eur J Pharmacol 76: 285–288, 1981.
Malbon CC, Hert RC, Fain JN: Characterization of [3H] adenosine binding to fat cell membranes. J Biol Cherm 253: 3114–3122, 1978.
Schwabe U, Kiffe H, Puchstein C, Trost T: Specific binding of [3H]adenosine to rat brain membranes. Naunyn Schmiedebergs Arch Pharmacol 310: 59–67, 1979.
Newman ME, Patel J, McIlwain H: The binding of[3H]adenosine to synaptosomal and other preparations from the mammalian brain. Biochem J 194: 611–620,1981.
Newman M, Levitzki A: Characteristics of high-affinity [3H]adenosine binding to rat brain synaptosomes and turkey erythrocyte membranes. Biochim Biophys Acta 685: 129–136, 1982.
Dutta P, Mustafa SJ: Saturable binding of adenosine to the dog heart microsomal fraction: competitive inhibition by aminophylline. J Pharmacol Exp Ther 211: 496–501, 1979.
Dutta P, Mustafa SJ: Binding of adenosine to the crude plasma membrane fraction isolated from dog coronary and carotid arteries. J Pharmacol Exp Ther 214: 496–502, 1980.
Schütz W, Brugger G: Characterization of [3H]-adenosine binding to media membranes of hog carotid arteries. Pharmacology 24: 26–34, 1982.
Daly JW, Nimitkitpaisan Y, Pons F, Bruns RF, Smellie F, Skolnick P: Binding sites for adenosine analogs: possible relationship to cyclic AMP-generating systems in brain tissue. Pharmacologist 21: 253, 1979 (abst).
Williams M, Risley EA: Binding of 3H-adenyl-5′-imidodiphosphate (AppNHp) to rat brain synaptic membranes. Fed Proc Fed Am Soc Exp Biol 39: 1009, 1980 (abst).
Bruns RF, Daly JW, Snyder SH: Adenosine receptors in brain membranes: Binding ofN6-cyciohexyl[3H]adenosine and 1,3-diethyl-8-[3H]phenylxanthine. Proc Natl Acad Sci USA 77: 5547–5551, 1980.
Schwabe U, Trost T: Characterization of adenosine receptors in rat brain by (−)[3H]N6-phenylisopropyladenosine. Naunyn Schmiedebergs Arch Pharmacol 313: 179–187, 1980.
Williams M, Risley EA: Biochemical characterization of putative central purinergic receptors by using 2-chloro[3H]adenosine, a stable analog of adenosine. Proc Natl Acad Sci USA 77: 6892–6896, 1980.
Wu PH, Phillis JW, Balls K, Rinaldi B: Specific binding of 2-[3H]chloroadenosine to rat brain cortical membranes. Can J Physiol Pharmacol 58: 576–579, 1980.
Clarke DA, Davoll J, Philips FS, Brown GB: Enzymatic deamination and vasodepressor effects of adenosine analogs. J Pharmacol Exp Ther 106: 291–302, 1952.
Westermann E, Stock K: Inhibitors of lipolysis: Potency and mode of action of α- and β- adrenolytics, methoxamine derivatives, prostaglandin E1 and phenylisopropyl adenosine, in Jeanrenaud B, Hepp D (eds): Adipose Tissue Regulation and Metabolic Functions. Stuttgart, Georg Thieme Verlag, 1970, pp 47–54.
Vapaatalo H, Onken D, Neuvonen PJ, Westermann E: Stereospecificity in some central and circulatory effects of phenylisopropyl-adenosine (PIA). Arzneim Forsch 25: 407–410, 1975.
Londos C, Cooper DMF, Schlegel W, Rodbell M: Adenosine analogs inhibit adipocyte adenylate cyclase by a GTP-dependent process: Basis for actions of adenosine and methylxanthines on cyclic AMP production and lipolysis. Proc Natl Acad Sci USA 75: 5362–5366, 1978.
Cooper DMF, Londos C, Rodbell M: Adenosine receptor-mediated inhibition of rat cerebral cortical adenylate cyclase by a GTP-dependent process. Mol Pharmacol 18: 598–601, 1980.
Stein HH, Somani P, Prasad RN: Cardiovascular effects of nucleoside analogs. Ann NY Acad Sci 255: 380–389, 1975.
Raberger G, Schütz W, Kraupp O: Coronary dilatory action of adenosine analogues: A comparative study. Arch Int Pharmacodyn Ther 230: 140–149, 1977.
Trost T, Schwabe U: Adenosine receptors in fat cells: Identification by (−)-N6-[3H]phenylisopropyladenosine binding. Mol Pharmacol 19: 228–235, 1981.
Gavish M, Goodman RR, Snyder SH: Solubilized adenosine receptors in the brain: Regulation by guanine nucleotides. Science 215: 1633–1635, 1982.
Goodman RR, Cooper MJ, Gavish M, Snyder SH: Guanine nucleotide and cation regulation of the binding of [3H]cyclohexyladenosine and [3H]diethylphenylxanthine to adenosine A1 receptors in brain membranes. Mol Pharmacol 21: 329–335, 1982.
Patel J, Marangos PJ, Stivers J, Goodwin K: Characterization of adenosine receptors in brain using N6-cyciohexyl[3H]adenosine. Brain Res 237: 203–214, 1982.
Murphy KM, Snyder SH: Adenosine receptors in rat testes: Labeling with 3H-cyclohexyladenosine. Life Sci 28: 917–920, 1981.
Lenschow V, Schwabe U: Effects of guanine nucleotides on adenosine receptors in rat brain. Naunyn Schmiedebergs Arch Pharmacol 319 (Suppl):R6, 1982 (abst).
Schütz W, Tuisl E, Kraupp O: Adenosine receptor agonists: Binding and adenylate cyclase stimulation in rat liver plasma membranes. Naunyn Schmiedebergs Arch Pharmacol 319: 34–39, 1982.
Grandt R, Gabel G, Jakobs KH: Guanine nucleotides and monovalent cations Increase affinities of adipocyte prostaglandin E2 and adenosine receptors for agonists. Naunyn Schmiedebergs Arch Pharmacol 319 (Suppl):R30 1982 (abst).
Haslam RJ, Cusack NJ: Blood platelet receptor for ADP and for adenosine, in Burnstock G (ed): Purinergic Receptors. London, Chapman & Hall, 1981, pp 223–285.
Cusack NJ, Hourani SMO: 5′-N-Ethylcarboxamidoadenosine: A potent inhibitor of human platelet aggregation. Br J Pharmacol 72: 443–447, 1981.
Lenschow, V., Hiittemann, E., Ukena, D., Schwabe, U.: Study of Ra adenosine receptors in human platelets by radioligand binding. Naunyn-Schmiedeberg’s Arch Pharmacol 321(Suppl): R 31, 1982 (abst).
Ukena, D., Martens, D., Schwabe, U.: Specific binding of 5′-N-ethylcarboxamido[3H]adenosine to calf thymocyte membranes. Naunyn Schmiedeberg’s Arch Pharmacol 321 (Suppl): R 38, 1982 (abst).
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© 1983 Martinus Nijhoff Publishers, The Hague
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Schwabe, U. (1983). General Aspects of Binding of Ligands to Adenosine Receptors. In: Berne, R.M., Rall, T.W., Rubio, R. (eds) Regulatory Function of Adenosine. Developments in Pharmacology, vol 2. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-3909-0_6
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DOI: https://doi.org/10.1007/978-1-4613-3909-0_6
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