Relative efficacy and potency of β-adrenoceptor agonists for generating cAMP in human lymphocytes

Drew A. MacGregor, Richard C. Prielipp, John F. Butterworth IV, Robert L. James, Roger L. Royster

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

Background: Dopexamine and dobutamine are traditionally described as having primarily β2-adrenergic agonist properties; norepinephrine is generally classified as β1-selective; and epinephrine, isoproterenol, and dopamine are considered mixed β1- and β2-receptor agonists. Much of this selectivity is designated froth studies conducted with intact cardiovascular systems in which indirect actions (eg, norepinephrine release from presynaptic nerve terminals) are not separated from direct agonist-receptor interactions. Objective: To assess the relative efficacy and potency of dopamine, dobutamine, dopexamine, epinephrine, isoproterenol, and norepinephrine for directly stimulating cyclic adenosine monophosphate (cAMP) production in human lymphocytes, a model of β2-adrenoceptor function. Design: Open-label, prospective paired studies of lymphocytes from nine healthy human volunteers (seven men). Setting: Experimental laboratory of a large, university-affiliated medical center. Interventions: Concentration- response curves were generated for each adrenergic agonist; maximal cAMP production was used to compare efficacy. For the agonists that more than doubled basal cAMP concentrations, EC50 calculations were used to compare potency. Measurements and main results: Isoproterenol and epinephrine produced the greatest concentrations of cAMP of the agonists tested. cAMP production was increased by isoproterenol at concentrations 1/10 to 1/10,000 that of the other agonists. Norepinephrine stimulated cAMP production only one third as much as epinephrine and isoproterenol, but more than double the level of dopamine, dobutamine, and dopexamine. EC50 concentrations for norepinephrine were, 10-fold higher than epinephrine and 50-fold higher than isoproterenol. Conclusions: Epinephrine and isoproterenol are the most efficacious and potent direct-acting β2-adrenergic receptor agonists using this lymphocyte cAMP model. Norepinephrine exhibits significant effects on the β-receptors on lymphocytes, suggesting β2-adrenoceptor effects with high concentrations of this drug. The very low cAMP levels generated by dopamine, dobutamine, and dopexamine (even in high concentrations) support other evidence that these agents have little direct effect on the β2- adrenoceptor.

Original languageEnglish (US)
Pages (from-to)194-200
Number of pages7
JournalCHEST
Volume109
Issue number1
DOIs
StatePublished - Jan 1 1996
Externally publishedYes

Keywords

  • dobutamine
  • dopexamine
  • epinephrine
  • inotropes
  • isoproterenol
  • lymphocyte s
  • β-adrenergic agonists

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