Introduction to Specific Drug Action and Membrane Surface Phenomena

  • Ronald J. Tallarida
  • Robert B. Raffa
  • Paul McGonigle
Part of the Springer Series in Pharmacologic Science book series (SSPHARMACOL)


Drugs are believed to produce their effects on biological systems either by alteration of some physical property of the cell or by a specific chemical reaction between the drug and its receptor. Many drugs produce their effects by interacting with specific cellular receptors. A description of the mathematical analysis of the interaction of drugs with receptors can be found in Chapter 8. The present chapter presents only an outline of the general development of the drug-receptor concept and highlights those aspects of the development which are considered by many the “principles” underlying present conceptions of the drug-receptor interaction. A more recent development, the recognition of cell processes (e.g., membrane capping, coated pits, and coated vesicles) capable of modifying the number of cell-surface receptors, is described in more detail.


Coated Vesicle Extracellular Material Anesthetic Concentration Cell Surface Membrane Coated Structure 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Anderson RGW, Kaplan J: Receptor-mediated endocytosis, in: Modern Cell Biology. New York, Alan R Liss Inc, 1983, pp 1–52.Google Scholar
  2. 2.
    Ariëns EJ: Affinity and intrinsic activity in the theory of competitive inhibition. Arch Int Pharmacodyn Ther 1954; 99:32–50.PubMedGoogle Scholar
  3. 3.
    Ariëns EJ, Beld AJ: The receptor concept in evolution. Biochem Pharmacol 1977; 26:913–918.PubMedCrossRefGoogle Scholar
  4. 4.
    Ariëns EJ: Receptors: from fiction to fact. Trends In Pharmacological Sciences 1979; 1:11–15.CrossRefGoogle Scholar
  5. 5.
    Barrow GM: Physical Chemistry. New York, McGraw-Hill, 1966, pp 753–768.Google Scholar
  6. 6.
    Belleau B: Conformational perturbation in relation to the regulation of enzymes and receptor behavior. Adv Drug Res 1965; 2:89–127.PubMedGoogle Scholar
  7. 7.
    Biscar JP: Photon enzyme activation. Bull Math Biol 1976; 38:29–38.PubMedGoogle Scholar
  8. 8.
    Bourguignon LYW, Singer SJ: Transmembrane interactions and the mechanism of capping of surface receptors by their specific ligands. Proc Natl Acad Sci USA 1971; 74:5031–5035.CrossRefGoogle Scholar
  9. 9.
    Clark AJ: The reaction between acetyl choline and muscle cells. J Physiol (Lond) 1926; 61:530–546.Google Scholar
  10. 10.
    Clark AJ: The antagonism of acetylcholine by atropine. J Physiol (Lond) 1926; 61:547–556.Google Scholar
  11. 11.
    Cope FW: A theory of enzyme kinetics based on electron conduction through the enzymatic particles, with applications to cytochrome oxidases and to free radical decay in melanin. Arch Biochem Biophys 1963; 103:352–365.PubMedCrossRefGoogle Scholar
  12. 12.
    Cope FW: A review of the applications of solid state physics concepts to biological systems. J Biol Phys 1975; 3:1–41.CrossRefGoogle Scholar
  13. 13.
    Cuatrecasas P: Membrane receptors. Ann Rev Biochem 1974; 43:169–214.PubMedCrossRefGoogle Scholar
  14. 14.
    Dean PM: Drug-receptor recognition: electrostatic field lines at the receptor and dielectric effects. Br J Pharmacol 1981; 74:39–46.PubMedGoogle Scholar
  15. 15.
    Dean PM: Drug-receptor recognition: molecular orientation and dielectric effects. Br J Pharmacol 1981; 74:47–60.PubMedGoogle Scholar
  16. 16.
    DeMeyts P, Rousseau GG: Receptor concepts—a century of evolution. Circ Res 1980; (suppl I) 46:13–19.Google Scholar
  17. 17.
    Eggers DF Jr, Gregory NW, Halsey GD Jr, et al: Physical Chemistry. New York, John Wiley & Sons, 1964, pp 739–741.Google Scholar
  18. 18.
    Enns CA, Larrick JN, Suomalainen H, et al: Co-migration and internalization of transferrin and its receptor on K562 cells. J Cell Biol 1983; 97:579–585.PubMedCrossRefGoogle Scholar
  19. 19.
    Fawcett DW: Surface specializations of absorbing cells. J Histochem Cytochem 1965; 13:75–91.PubMedCrossRefGoogle Scholar
  20. 20.
    Fehlman M, Carpenter J-L, LeCam A, et al: Biochemical and morphological evidence that the insulin receptor is internalized with insulin in hepatocytes. J Cell Biol 1982; 93:82–87.CrossRefGoogle Scholar
  21. 21.
    Ferguson J: The use of chemical potentials as indices of toxicity. Proc Soc (Lond) 1939; 127B:387–404.CrossRefGoogle Scholar
  22. 22.
    Friend DS, Farquhar MG: Functions of coated vesicles during protein absorption in the rat vas deferens. J Cell Biol 1967; 35:357–375.PubMedCrossRefGoogle Scholar
  23. 23.
    Furchgott RF: The use of β-haloalkylamines in the differentiation of receptors and in the determination of dissociation constants. Adv Drug Res 1966; 3:21–25.Google Scholar
  24. 24.
    Gaddum JH: The action of adrenaline and ergotamine on the uterus of the rabbit. J Physiol (Lond) 1926; 61:141–150.Google Scholar
  25. 25.
    Ganjian F, Cutie AJ, Jochsberger T: In vitro adsorption studies of Cimetidine. J Phar-maceut Sci 1980; 69:352–353.CrossRefGoogle Scholar
  26. 26.
    Gero A: Interactions of narcotics and their antagonists with human serum esterase— IV. drug-receptor interaction at the acceleratory site. Arch Int Pharmacodyn Ther 1973; 206:41–46.PubMedGoogle Scholar
  27. 27.
    Gershon ND: Model for capping of membrane receptors based on boundary surface effects. Proc Natl Acad Sci USA 1978; 75:1357–1360.PubMedCrossRefGoogle Scholar
  28. 28.
    Goldstein JL, Anderson GW, Brown MS: Coated pits, coated vesicles, and receptor-mediated endocytosis. Nature 1979; 279:679–685.PubMedCrossRefGoogle Scholar
  29. 29.
    Harding C, Heuser J, Stahl P: Receptor-mediated endocytosis of transferrin and recycling of the transferrin receptor in rat reticulocytes. J Cell Biol 1983; 97:329–339.PubMedCrossRefGoogle Scholar
  30. 30.
    Heuser JE, Reese TS: Evidence for recycling of synaptic vesicle membrane during transmitter release at the frog neuromuscular junction. J Cell Biol 1973; 57:315–344.PubMedCrossRefGoogle Scholar
  31. 31.
    Hill AV: The mode of action of nicotine and curari determined by the form of the contraction curve and the method of temperature coefficients. J Physiol (Lond) 1909; 39:361–373.Google Scholar
  32. 32.
    Hill CM, Waight RD, Bardsley WG. Does any enzyme follow the Michaelis-Menten equation? Mol Cell Biol 1977; 15:173–178.Google Scholar
  33. 33.
    Kaneseki T, Kadota K: The “Vesicle in a basket”. J Cell Biol 1969; 42:202–220.CrossRefGoogle Scholar
  34. 34.
    Karlin AJ: On the application of a “plausible model” of allosteric proteins to the receptor for acetylcholine. J Theor Biol 1967; 16:306.PubMedCrossRefGoogle Scholar
  35. 35.
    Kelly WG, Passaniti A, Woods JW, et al: Tubulin as a molecular component of coated vesicles. J Cell Biol 1983; 97:1191–1199.PubMedCrossRefGoogle Scholar
  36. 36.
    Koshland DE: The Enzymes, vol 1; Boyer PD, Myrback K, Lardy H (eds) New York, Academic Press, 1958, p 305.Google Scholar
  37. 37.
    Langley JN: On the physiology of the salivary secretion, pt II. J Physiol 1878; 1:339–369.PubMedGoogle Scholar
  38. 38.
    Langmuir I: The adsorption of gases on plane surfaces of glass, mica and platinum. J Am Chem Soc 1918; 40:1361–1403.CrossRefGoogle Scholar
  39. 39.
    Linden CD, Roth TF, Dedman JR: The association of calmodulin with coated vesicles. J Cell Biol 1979; 83:289a.Google Scholar
  40. 40.
    Monod J, Wyman J, Changeux JP: On the nature of allosteric transitions: a plausible model. J Mol Biol 1965; 12:88–118.PubMedCrossRefGoogle Scholar
  41. 41.
    Murphy TL, Decker G, August JT: Glycoproteins of coated pits, cell junctions, and the entire cell surface revealed by monoclonal antibodies and immuno-microscopy. J Cell Biol 1983; 97:533–541.PubMedCrossRefGoogle Scholar
  42. 42.
    Pastan IH, Willingham MC: Receptor-mediated endocytosis of hormones in cultured cells. Ann Rev Physiol 1981; 43:239–250.CrossRefGoogle Scholar
  43. 43.
    Pearse BMF: Coated vesicles from pig brain: purification and biochemical characterization. J Mol Biol 1975; 97:93–98.PubMedCrossRefGoogle Scholar
  44. 44.
    Perry RH, Chilton CH, Kirkpatrick SD: Chemical Engineer’s Handbook. New York, McGraw-Hill, 1963, p 16–8.Google Scholar
  45. 45.
    Pickard NA, Gruemer H-D, Verrill HL, et al: Systemic membrane defect in the proximal muscular dystrophies. N Engl J Med 1978; 299:841–846.PubMedCrossRefGoogle Scholar
  46. 46.
    Pilch PF, Shia MA, Benson RJJ, et al: Coated vesicles participate in the receptor-mediated endocytosis of insulin. J Cell Biol 1983; 93:133–138.CrossRefGoogle Scholar
  47. 47.
    Rosenbluth J, Wissig SL: The uptake of ferritin by toad spinal ganglion cells. J Cell Biol 1963; 19:91A.Google Scholar
  48. 48.
    Rosenbluth J, Wissig SL: The distribution of exogenous ferritin in toad spinal ganglia and the mechanism of its uptake by neurons. J Cell Biol 1964; 23:307–325.PubMedCrossRefGoogle Scholar
  49. 49.
    Roth TF, Porter KR: Yolk protein uptake in the oocyte of the mosquito aedes aegypti L. J Cell Biol 1964; 20:313–332.PubMedCrossRefGoogle Scholar
  50. 50.
    Salisbury JL, Condeelis JS, Satir P: Role of coated vesicles, microfilaments, arid calmodulin in receptor-mediated endocytosis by cultured B lymphoblastoid cells. J Cell Biol 1980; 87:132–141.PubMedCrossRefGoogle Scholar
  51. 51.
    Salpeter MM, Harris R: Distribution and turnover rate of acetylcholine receptors throughout the junctional folds at a vertebrate neuromuscular junction. J Cell Biol 1983; 96:1781–1785.PubMedCrossRefGoogle Scholar
  52. 52.
    Schild HO: pA, a new scale for the measurement of drug antagonism. Br J Pharmacol 1947; 2:189–206.Google Scholar
  53. 53.
    Schlessinger J, Shechter Y, Cuatrecasas P, et al; Quantitative determination of the lateral diffusion coefficients of the hormone-receptor complexes of insulin and epidermal growth factor on the plasma membrane of cultured fibroblasts. Proc Natl Acad Sci USA 1978; 75:5353–5357.PubMedCrossRefGoogle Scholar
  54. 54.
    Schreiner GF, Unanue ER: Membrane and cytoplasmic changes in B lymphocytes induced by ligand-surface immunoglobulin interaction. Adv Immunol 1976; 24:37–165.PubMedCrossRefGoogle Scholar
  55. 55.
    Schreiner GF, Fujiwara K, Pollard TD, et al; Redistribution of myosin accompanying capping of surface Ig. J Exp Med 1977; 145:1393–1398.PubMedCrossRefGoogle Scholar
  56. 56.
    Smith JM: Chemical Engineering Kinetics. New York, McGraw-Hill, 1970, pp 329–335.Google Scholar
  57. 57.
    Steinman RM, Mellman IS, Muller WA, et al: Endocytosis and the recycling of plasma membrane. J Cell Biol 1983; 96:1–27.PubMedCrossRefGoogle Scholar
  58. 58.
    Stephenson RP: A modification of receptor theory. Br J Pharmacol 1956; 11:379–393.Google Scholar
  59. 59.
    Tallarida RJ, Harakal C, Rusy BF, et al: Theoretical basis for the determination of the molecularity of drug-receptor reactions and affinity of agonists. Curr Mod Biol 1968; 2:249–253.PubMedGoogle Scholar
  60. 60.
    Thron CD. On the analysis of pharmacological experiments in terms of an allosteric receptor model. Mol Pharmacol 1973; 9:1–9.PubMedGoogle Scholar
  61. 61.
    Ungewickell E, Branton D: Triskelions: the building blocks of clathrin coats. Trends In Biochemical Sciences 1982; 7:358–361.CrossRefGoogle Scholar
  62. 62.
    Zaremba S, Keen JH: Assembly polypeptides from coated vesicles mediate reassembly of unique clathrin coats. J Cell Biol 1983; 97:1339–1347.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag New York Inc. 1988

Authors and Affiliations

  • Ronald J. Tallarida
    • 1
  • Robert B. Raffa
    • 1
    • 2
    • 3
  • Paul McGonigle
    • 4
  1. 1.Department of PharmacologyTemple University School of MedicinePhiladelphiaUSA
  2. 2.Janssen Research FoundationUSA
  3. 3.Jefferson Medical CollegePhiladelphiaUSA
  4. 4.Department of PharmacologyUniversity of Pennsylvania School of MedicinePhiladelphiaUSA

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