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. 1972 Aug;51(8):2124–2129. doi: 10.1172/JCI107019

Effects of catecholamines and adrenergic-blocking agents on plasma and urinary cyclic nucleotides in man

John H Ball 1,2, Neil I Kaminsky 1,2, Joel G Hardman 1,2, Arthur E Broadus 1,2, Earl W Sutherland 1,2, Grant W Liddle 1,2
PMCID: PMC292369  PMID: 4403383

Abstract

Studies were performed in healthy volunteers to determine the effects of catecholamines and adrenergic-blocking agents on plasma and urinary levels of adenosine 3′,5′-monophosphate (cyclic AMP) and guanosine 3′,5′-monophosphate (cyclic GMP).

Plasma cyclic AMP rose in response to infusions of the β-adrenergic agent, isoproterenol, or in response to infusions of either epinephrine or norepinephrine alone or in combination with the α-adrenergic-blocking agent, phentolamine. Although urinary cyclic AMP also rose, the percentage increase was less than that observed in the plasma. These treatments caused no increase in plasma cyclic GMP.

Plasma cyclic GMP rose in response to infusions of α-adrenergic agents, viz., epinephrine or norepinephrine infused together with the β-blocking agent, propranolol. These treatments caused no increase in plasma cyclic AMP.

These observations are consistent with the current concept that the actions of β-adrenergic agents are mediated by increases in cyclic AMP formation in target tissues. Such a mediating role has not been established for cyclic GMP, but the data suggest the possibility that cyclic GMP metabolism is responsive either to α-adrenergic stimulation or to parasympathetic stimulation which occurs as a reflexive consequence of the pressor effect of α-adrenergic agents.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Broadus A. E., Kaminsky N. I., Hardman J. G., Sutherland E. W., Liddle G. W. Kinetic parameters and renal clearances of plasma adenosine 3',5'-monophosphate and guanosine 3',5'-monophosphate in man. J Clin Invest. 1970 Dec;49(12):2222–2236. doi: 10.1172/JCI106441. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Broadus A. E., Kaminsky N. I., Northcutt R. C., Hardman J. G., Sutherland E. W., Liddle G. W. Effects of glucagon on adenosine 3',5'-monophosphate and guanosine 3',5'-monophosphate in human plasma and urine. J Clin Invest. 1970 Dec;49(12):2237–2245. doi: 10.1172/JCI106442. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Chase L. R., Aurbach G. D. Parathyroid function and the renal excretion of 3'5'-adenylic acid. Proc Natl Acad Sci U S A. 1967 Aug;58(2):518–525. doi: 10.1073/pnas.58.2.518. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. George W. J., Polson J. B., O'Toole A. G., Goldberg N. D. Elevation of guanosine 3',5'-cyclic phosphate in rat heart after perfusion with acetylcholine. Proc Natl Acad Sci U S A. 1970 Jun;66(2):398–403. doi: 10.1073/pnas.66.2.398. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Hardman J. G., Davis J. W., Sutherland E. W. Effects of some hormonal and other factors on the excretion of guanosine 3',5'-monophosphate and adenosine 3',5'-monophosphate in rat urine. J Biol Chem. 1969 Dec 10;244(23):6354–6362. [PubMed] [Google Scholar]
  6. Kaminsky N. I., Broadus A. E., Hardman J. G., Jones D. J., Jr, Ball J. H., Sutherland E. W., Liddle G. W. Effects of parathyroid hormone on plasma and urinary adenosine 3',5'-monophosphate in man. J Clin Invest. 1970 Dec;49(12):2387–2395. doi: 10.1172/JCI106458. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Kuo J. F., Lee T. P., Reyes P. L., Walton K. G., Donnelly T. E., Jr, Greengard P. Cyclic nucleotide-dependent protein kinases. X. An assay method for the measurement of quanosine 3',5'-monophosphate in various biological materials and a study of agents regulating its levels in heart and brain. J Biol Chem. 1972 Jan 10;247(1):16–22. [PubMed] [Google Scholar]
  8. Levine R. A., Dixon L. M., Franklin R. B. Effects of exogenous adenosine 3',5'-monophosphate in man. I. Cardiovascular responses. Clin Pharmacol Ther. 1968 Mar-Apr;9(2):168–179. doi: 10.1002/cpt196892168. [DOI] [PubMed] [Google Scholar]
  9. Robison G. A., Butcher R. W., Sutherland E. W. Adenyl cyclase as an adrenergic receptor. Ann N Y Acad Sci. 1967 Feb 10;139(3):703–723. doi: 10.1111/j.1749-6632.1967.tb41239.x. [DOI] [PubMed] [Google Scholar]
  10. Robison G. A., Sutherland E. W. Sympathin E, sympathin I, and the intracellular level of cyclic AMP. Circ Res. 1970 Jul;27(1 Suppl 1):147–161. [PubMed] [Google Scholar]
  11. Sutherland E. W., Robison G. A. The role of cyclic-3',5'-AMP in responses to catecholamines and other hormones. Pharmacol Rev. 1966 Mar;18(1):145–161. [PubMed] [Google Scholar]

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