The Vascular (DA1) Dopamine Receptor

  • Jai D. Kohli
  • Leon I. Goldberg
Part of the Satellite Symposia of the IUPHAR 10th International Congress of Pharmacology book series


Investigation of the unusual cardiovascular effects of DA by Goldberg and colleagues in the 1960s led to the hypothesis of a specific DA receptor which mediated vasodilatation in the renal and mesenteric vascular beds of the dog (Goldberg, 1972). In the 1970s the action of drugs on the postganglionic sympathetic nerves modulating the release of the transmitter via the presynaptic receptors was discovered (Langer, 1977, 1980; Starke, 1977). In the course of the investigation of presynaptic alpha-adrenoceptors, Langer (1973) and McCulloch et al. (1973) obtained evidence for the presence of specific DA receptors on sympathetic nerve terminals.


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  1. Berkowitz, B. A. and Ohlstein, E. H. (1984). Cardiovascular dopamine receptors: Recent advances in agonists and antagonists of the DA1-receptor. J. Cardiovasc. Pharmac., 6, S559–S563CrossRefGoogle Scholar
  2. Brodde, O.-E. (1982). Vascular dopamine receptors: Demonstration and characterization by in vitro studies. Life Sci., 31, 289–306PubMedCrossRefGoogle Scholar
  3. Brown, R. A., Hall, J. C., Humphries, R. G., O’Connor, S. E., Smith, G. W. and Verity, A. (1983a). Peripheral dopamine receptors: Agonist potencies in different models. In Carlsson, A. and Nilsson, J. L. G. (Eds.), Dopamine Receptor Agonists, Swedish Pharmaceutical Press, Stockholm, pp. 195–197Google Scholar
  4. Brown, R. A., O’Connor, S. E., Smith, G. W. and Verity, A. (1983b). The rabbit isolated arterially perfused intestinal segment preparation: A model for vascular dopamine receptors. J. Pharmac. Methods, 9, 137–145CrossRefGoogle Scholar
  5. Cannon, J. G. (1983). Structure-activity relationships of dopamine agonists. Ann. Rev. Pharmac. Toxicol., 23, 103–130CrossRefGoogle Scholar
  6. Carlsson, A. and Nilsson, J. L. G. (Eds.) (1983). Dopamine Receptor Agonists, Swedish Pharmaceutical Press, StockholmGoogle Scholar
  7. Costall, B., Lim, S. K., Naylor, R. J. and Cannon, J. G. (1982). On the preferred rotameric conformation for dopamine agonist action: an illusory quest? J. Pharm. Pharmac., 34, 246–254CrossRefGoogle Scholar
  8. Crumly, H. J., Jr., Pinder, R. M., Hinshaw, W. B. and Goldberg, L. I. (1976). Dopamine-like renal and mesenteric vasodilation caused by apomorphine 6-propylnorapomorphine and 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaph-thalene. Nature, Lond., 259, 584–587CrossRefGoogle Scholar
  9. Dallas, S., Drew, G. M. and Hilditch, A. (1986). Effects of dopamine receptor agonists and antagonists at peripheral neuronal and vascular dopamine receptors in the anaesthetised cat. J. Cardiovasc. Pharmac., 8, 116–125CrossRefGoogle Scholar
  10. Glock, D., Goldberg, L. I. and Kohli, J. D. (1981). Differential peripheral dopamine (DA) receptor antagonism by intravenous injections of (R)- and (S)-sulpiride. Fed. Proc., 40, 290Google Scholar
  11. Goldberg, L. I. (1972). Cardiovascular and renal actions of dopamine: Potential clinical applications. Pharmac. Rev., 24, 1–29Google Scholar
  12. Goldberg, L. I., Glock, D., Kohli, J. D. and Barnett, A. (1984). Separation of peripheral dopamine receptors by a selective DA1 antagonist, SCH 23390. Hypertension, 6, 125–130CrossRefGoogle Scholar
  13. Goldberg, L. I. and Kohli, J. D. (1979). Peripheral pre- and post-synaptic dopamine receptors: Are they different from dopamine receptors in the central nervous system? Commun. Psychopharmac., 3, 447–456Google Scholar
  14. Goldberg, L. I. and Kohli, J. D. (1981). Specific dopamine receptors in vascular smooth muscle. In Vanhoutte, P. M. and Leusen, I. (Eds.), Vasodilatation, Raven Press, New York, pp. 131–141Google Scholar
  15. Goldberg, L. I., Kohli, J. D. and Glock, D. (1986). Conclusive evidence for two subtypes of peripheral dopamine receptors. In Woodruff, G. N., Poat, J. A. and Roberts, P. J. (Eds.), Dopaminergic Systems and their Regulation, Macmillan, London, pp. 195–212Google Scholar
  16. Goldberg, L. I., Kohli, J. D. and Listinsky, J. J. (1979a). Comparison of peripheral pre- and post-synaptic dopamine receptors. In Langer, S. Z., Starke, K. and Dubocovich, M. L. (Eds.), Presynaptic Receptors, Pergamon Press, Paris, pp. 37–41Google Scholar
  17. Goldberg, L. I., Kohli, J. D., Listinsky, J. J. and McDermed, J. D. (1979b). Structure activity relationships of pre- and post-synaptic dopamine receptors mediating vasodilation. In Usdin, E., Kopin, I. J. and Barchas, J. (Eds.), Catecholamines: Basic and Clinical Frontiers, Pergamon Press, New York, pp. 447–449CrossRefGoogle Scholar
  18. Goldberg, L. I. and Toda, N. (1975). Dopamine induced relaxation of isolated canine renal, mesenteric, and femoral arteries contracted with prostaglandin F. Circulation Res., 36, 197–1102CrossRefGoogle Scholar
  19. Goldberg, L. I., Volkman, P. H. and Kohli, J. D. (1978). A comparison of the vascular dopamine receptor with other dopamine receptors. Ann. Rev. Pharmac. Toxicol., 18, 57–79CrossRefGoogle Scholar
  20. Hahn, R. A., Wardell, J. R., Jr., Sarau, H. M. and Ridley, P. T. (1982). Characterization of the peripheral and central effects of SK&F 82526, a novel dopamine receptor agonist. J. Pharmac. Exp. Ther., 223, 305–313Google Scholar
  21. Hilditch, A. and Drew, G. M. (1981). Characteristics of the dopamine receptors in the rabbit isolated splenic artery. Eur. J. Pharmac., 72, 287–296CrossRefGoogle Scholar
  22. Hilditch, A. and Drew, G. M. (1984). Effects of dopamine receptor agonists and antagonists at peripheral neuronal and vascular dopamine receptors in the anaesthetised dog. J. Cardiovasc. Pharmac., 6, 460–469CrossRefGoogle Scholar
  23. Hilditch, A. and Drew, G. M. (1985a). Peripheral dopamine receptor subtypes—a closer look. Trends Pharmac. Sci., 6, 396–400CrossRefGoogle Scholar
  24. Hilditch, A. and Drew, G. M. (1985b). Peripheral dopamine receptor blockade by SCH 23390 and domperidone in vitro. Eur. J. Pharmac, 116, 171–174CrossRefGoogle Scholar
  25. Hughes, A. and Sever, P. (1987). Vascular dopamine receptors in isolated human umbilical artery. Xth International Congress of Pharmacology, Sydney, Australia Abstracts, P 757Google Scholar
  26. Ilhan, M., Long, J. P. and Cannon, J. G. (1975). Bulbocapnine’s ability to antagonize the adrenergic inhibitory action of dopamine and analogs. Eur. J. Pharmac, 33, 13–18CrossRefGoogle Scholar
  27. Iorio, L. C., Barnett, A., Leitz, F. H., Houser, V. P. and Korduba, C. A. (1983). SCH 23390, a potential benzazepine antipsychotic with unique interactions on dopaminergic systems. J. Pharmac. Exp. Ther., 226, 462–468Google Scholar
  28. Kaiser, C. and Jain, T. (1985). Dopamine receptors: Functions, subtypes and emerging concepts. Med. Res. Rev., 5, 145–229PubMedCrossRefGoogle Scholar
  29. Kohli, J. D., Glock, D. and Goldberg, L. I. (1985). Effects of the enantiomers of 3-PPP on DA1 and DA2 dopamine receptors in the dog. Eur. J. Pharmac., 114, 305–310CrossRefGoogle Scholar
  30. Kohli, J. D., Glock, D. and Goldberg, L. I. (1986). Bulbocapnine is not a selective DA1 receptor antagonist. J. Pharm. Pharmac, 38, 401–402CrossRefGoogle Scholar
  31. Kohli, J. D. and Goldberg, L. I. (1980). Effects of 3′,4′-dihydroxynomifensine on the dopamine vascular receptor. J. Pharm. Pharmac, 32, 225–226CrossRefGoogle Scholar
  32. Kohli, J. D. and Goldberg, L. I. (1987). Dopamine receptors: A classification based on physiological studies. In Creese, I. and Fraser, C. M. (Eds.), Dopamine Receptors, Alan R. Liss, New York, pp. 97–114Google Scholar
  33. Kohli, J. D., Goldberg, L. I. and McDermed, J. D. (1982). Modification of cardiovascular actions of 2-amino-5,6-dihydroxytetralin by N, N-di-n-propyl substitution. Eur. J. Pharmc., 81, 293–299CrossRefGoogle Scholar
  34. Kohli, J. D., Goldberg, L. I. and Nand, N. (1979a). 1-Aminomethyl isochromans: New vascular dopamine agonists. Pharmacologist, 21, 202Google Scholar
  35. Kohli, J. D., Goldberg, L. I. and Nichols, D. E. (1979b). Dopamine vascular actions of N-substituted derivatives of 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaph-thalene (ADTN). Eur. J. Pharmac., 56, 39–44CrossRefGoogle Scholar
  36. Kohli, J. D., Goldberg, L. I., Volkman, P. H. and Cannon, J. G. (1978). N, N-di-n-Propyl dopamine: A qualitatively different dopamine vascular agonist. J. Pharmac. Exp. Ther., 207, 16–22Google Scholar
  37. Kohli, J. D., Listinsky, J. J. and Goldberg, L. I. (1979c). The inhibitory neurogenic effects of N-N-di-n-propyl dopamine: a vascular dopamine agonist. In Imbs, J. L. and Schwartz, J. (Eds.), Peripheral Dopaminergic Receptors, Pergamon Press, Paris, pp. 249–255CrossRefGoogle Scholar
  38. Kohli, J. D., Weder, A. B., Goldberg, L. I. and Ginos, J. Z. (1980). Structure activity relationships of N-substituted dopamine derivatives as agonists of the dopamine vascular and other cardiovascular receptors. J. Pharmac. Exp. Ther., 213, 370–374Google Scholar
  39. Kohli, J. D., Weinstock, J., Glock, D. and Goldberg, L. I. (1987). Dopamine receptor activities of benzothiazol-2-one analogs of dopamine. Xth International Congress of Pharmacology, Sydney, Australia (Abstracts P 1311)Google Scholar
  40. Kumar, A., Khanna, J. M., Jain, P. C., Anand, N., Srimal, R. C., Kohli, J. D. and Goldberg, L. (1987). Catecholamines in a semi-rigid framework: Synthesis and biological activities of N-substituted 1-aminomethyl-5,6- and 6,7-dihydroxyiso-chromans. Indian J. Chem., 26B, 47–51Google Scholar
  41. Langer, S. Z. (1973). The regulation of transmitter release elicited by nerve stimulation through a presynaptic feed-back mechanism. In Usdin, E. and Snyder, S. H. (Eds.), Frontiers in Catecholamine Research, Pergamon Press, Oxford, pp. 543–549CrossRefGoogle Scholar
  42. Langer, S. Z. (1977). Presynaptic receptors and their role in the regulation of transmitter release. Br. J. Pharmac., 60, 481–497CrossRefGoogle Scholar
  43. Langer, S. Z. (1980). Presynaptic regulation of the release of catecholamines. Pharmac. Rev., 32, 337–362Google Scholar
  44. Lokhandwala, M. F. and Jandhyala, B. S. (1979). The role of sympathetic nervous system in the vascular actions of dopamine. J. Pharmac. Exp. Ther., 210, 120–126Google Scholar
  45. McCulloch, M. W., Rand, M. J. and Story, D. F. (1973). Evidence for a dopaminergic mechanism for modulation of adrenergic transmission in the rabbit ear artery. Br. J. Pharmac, 49, 141P–142PCrossRefGoogle Scholar
  46. Missale, C., Pizzi, M., Memo, M., Picotti, G. B., Carruba, M. O. and Spano, P. F. (1985). Postsynaptic D1 and D2 dopamine receptors are present in rabbit renal and mesenteric arteries. Neurosci. Lett., 61, 207–211PubMedCrossRefGoogle Scholar
  47. Nichols, D. E. (1983). The development of novel dopamine agonists. In Kaiser, C. and Kebabian, J. W. (Eds.), Dopamine Receptors, American Chemical Company, Washington, DC, pp. 201–218CrossRefGoogle Scholar
  48. Ohlstein, E. H., Zabko-Potapovich, B. and Berkowitz, B. A. (1984). Studies on vascular dopamine receptors with the dopamine receptor agonist: SK&F 82526. J. Pharmac. Exp. Ther., 229, 433–439Google Scholar
  49. Ohlstein, E. H., Zabko-Potapovich, B. and Berkowitz, B. A. (1985). The DA1 receptor agonist fenoldopam (SK&F 82526) is also an alpha2-adrenoceptor antagonist. Eur. J. Pharmac., 118, 321–329CrossRefGoogle Scholar
  50. Schmidt, M., Imbs, J.-L., Giesen-Crouse, E.-M. and Schwartz, J. (1985). Effects of SK&F 82526 and SK&F 83742 on the renal vascular dopamine receptor. J. Pharmac, Paris, 16, 15–22Google Scholar
  51. Schmidt, M., Imbs, J.-L., Neumeyer, J. L., Giesen, E.-M. and Schwartz, J. (1984). Vascular effects of apomorphine and related compounds in the perfused rat kidney. Eur. J. Pharmac., 97, 75–85CrossRefGoogle Scholar
  52. Schmidt, M., Imbs, J.-L. and Schwartz, J. (1981). The vascular dopamine receptor: A review. J. Pharmac, Paris, 12, 355–382Google Scholar
  53. Setler, P. E., Pendleton, R. G. and Finlay, E. (1975). The cardiovascular actions of dopamine and the effects of central and peripheral catecholaminergic receptor blocking drugs. J. Pharmac Exp. Ther., 192, 702–712Google Scholar
  54. Shepperson, N. B., Duval, N., Massingham, R. and Langer, S. Z. (1982). Differentia! blocking effects of several dopamine receptor antagonists for peripheral pre- and postsynaptic dopamine receptors in the anesthetized dog. J. Pharmac Exp. Ther., 221, 753–761Google Scholar
  55. Starke, K. (1977). Regulation of noradrenaline release by presynaptic receptor systems. Rev. Physiol. Biochem. Pharmac., 77, 1–124Google Scholar
  56. Toda, N. (1976). Influence of dopamine and noradrenaline on isolated cerebral arteries of the dog. Br. J. Pharmac., 58, 121–126CrossRefGoogle Scholar
  57. Toda, N. (1983). Heterogeneity in the response to dopamine of monkey cerebral and peripheral arteries. Am. J. Physiol., 245, H930–H936Google Scholar
  58. Toda, N. and Goldberg, L. I. (1973). Dopamine-induced relaxation of isolated arterial strips. J. Pharm. Pharmac., 25, 587–589CrossRefGoogle Scholar
  59. Volkman, P. H. and Goldberg, L. I. (1976). Lack of correlation between inhibition of prolactin release and stimulation of dopaminergic renal vasodilation. Pharmacologist, 18, 130Google Scholar
  60. Volkman, P. H., Kohli, J. D., Goldberg, L. I., Cannon, J. G. and Lee, T. (1977). Conformational requirements for dopamine-induced vasodilation. Proc Natl Acad. Sci. U.S.A., 74, 3602–3606PubMedPubMedCentralCrossRefGoogle Scholar
  61. Weinstock, J., Gaitanopoulos, D. E., Stringer, O. D., Franz, R. G., Hieble, J. P., Kinter, L. B., Mann, W. A., Flaim, K. E. and Gessner, G. (1987). The synthesis and evaluation of non-catechol D-l and D-2 dopamine receptor agonists: Ben-zimidazol-2-one, benzoxazol-2-one and highly potent benzothiazol-2-one 7-ethylamines. J. Med. Chem., 30, 1166–1176PubMedCrossRefGoogle Scholar
  62. Weinstock, J., Hieble, J. P. and Wilson, J. W. III (1985). The chemistry and pharmacology of 3-benzazepine derivatives. Drugs of the Future, 10, 645–697Google Scholar

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© Jai D. Kohli and Leon I. Goldberg 1988

Authors and Affiliations

  • Jai D. Kohli
  • Leon I. Goldberg

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