Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1977 Nov;60(5):1141–1148. doi: 10.1172/JCI108866

Catecholamine Uptake, Accumulation, and Release in Acute Porphyria

M Flint Beal 1,2, Nuzhet O Atuk 1,2, Thomas C Westfall 1,2, Suzanne M Turner 1,2
PMCID: PMC372467  PMID: 908757

Abstract

Hypertension and tachycardia are well known features of acute porphyria and have been shown to be related to increased circulating catecholamines. The mechanism by which circulating catecholamines are increased was studied using the isolated perfused rat heart and human platelets as a model of adrenergic neuronal function. It was found that neither δ-aminolevulinate (ALA) nor porphobilinogen (PBG) blocked uptake or caused release in the isolated perfused rat heart. Platelets from six patients with acute prophyria, three in remission and three latent, with matching normal controls were studied with regard to their uptake of [3H]norepinephrine in the presence of ALA or PBG. It was found that ALA and PBG significantly reduced uptake and accumulation of [3H]-norepinephrine in patients with acute porphyria; however, no similar reduction in uptake and accumulation was observed in the platelets of normal controls. Therefore, it appears that there is a latent defect in the catecholamine uptake and (or) accumulation of platelets of patients with acute prophyria which only manifests itself in the presence of ALA or PBG. If platelet uptake serves as a model of adrenergic neuron uptake, this suggests that elevated circulating catecholamine levels during acute attacks of acute porphyria are caused at least partially by blockade of re-uptake into the sympathetic neurons.

Full text

PDF
1141

Selected References

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

  1. Abrams W. B., Solomon H. M. The human platelet as a pharmacologic model for the adrenergic neuron. The uptake and release of norepinephrine. Clin Pharmacol Ther. 1969 Sep-Oct;10(5):702–709. doi: 10.1002/cpt1969105702. [DOI] [PubMed] [Google Scholar]
  2. BORN G. V., BRICKNELL J. The uptake of 5-hydroxytryptamine by blood platelets in the cold. J Physiol. 1959 Jun 23;147(1):153–161. doi: 10.1113/jphysiol.1959.sp006230. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Barbeau A., Campanella G., Butterworth R. F., Yamada K. Uptake and efflux of 14-C-dopamine in platelets: evidence for a generalized defect in Parkinson's disease. Neurology. 1975 Jan;25(1):1–9. doi: 10.1212/wnl.25.1.1. [DOI] [PubMed] [Google Scholar]
  4. Beattie A. D., Moore M. R., Goldberg A., Ward R. L. Acute intermittent porphyria: response of tachycardia and hypertension to propranolol. Br Med J. 1973 Aug 4;3(5874):257–260. doi: 10.1136/bmj.3.5874.257. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Born G. V., Smith J. B. Uptake, metabolism and release of (3H)-adrenaline by human platelets. Br J Pharmacol. 1970 Aug;39(4):765–778. doi: 10.1111/j.1476-5381.1970.tb09903.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bygdeman S., Johnsen O. Studies on the effect of adrenergic blocking drugs on catecholamine-induced platelet aggregation and uptake of noradrenaline and 5-hydroxytryptamine. Acta Physiol Scand. 1969 Jan-Feb;75(1):129–138. doi: 10.1111/j.1748-1716.1969.tb04364.x. [DOI] [PubMed] [Google Scholar]
  7. Cheramy A., Besson M. J., Glowinski J. Increased release of dopane from striatal dopaminergic terminals in the rat after treatment with a neuroleptic: thioproperazine. Eur J Pharmacol. 1970 May;10(2):206–214. doi: 10.1016/0014-2999(70)90274-8. [DOI] [PubMed] [Google Scholar]
  8. Dhar G. J., Bossenmaier I., Petryka Z. J., Cardinal R., Watson C. J. Effects of hematin in hepatic porphyria. Further studies. Ann Intern Med. 1975 Jul;83(1):20–30. doi: 10.7326/0003-4819-83-1-20. [DOI] [PubMed] [Google Scholar]
  9. Doba N., Reis D. J. Role of central and peripheral adrenergic mechanisms in neurogenic hypertension produced by brainstem lesions in rat. Circ Res. 1974 Mar;34(3):293–301. doi: 10.1161/01.res.34.3.293. [DOI] [PubMed] [Google Scholar]
  10. Elder G. H., Evans J. O., Thomas N. The primary enzyme defect in hereditary coproporphyria. Lancet. 1976 Dec 4;2(7997):1217–1219. doi: 10.1016/s0140-6736(76)91143-0. [DOI] [PubMed] [Google Scholar]
  11. GIBSON J. B., GOLDBERG A. The neuropathology of acute porphyria. J Pathol Bacteriol. 1956 Apr;71(2):495–509. doi: 10.1002/path.1700710222. [DOI] [PubMed] [Google Scholar]
  12. GOLDBERG A. Acute intermittent porphyria: a study of 50 cases. Q J Med. 1959 Apr;28(110):183–209. [PubMed] [Google Scholar]
  13. GOLDBERG A., PATON W. D., THOMPSON J. W. Pharmacology of the porphyrins and porphobilinogen. Br J Pharmacol Chemother. 1954 Mar;9(1):91–94. doi: 10.1111/j.1476-5381.1954.tb00822.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Goldberg A., Rimington C., Lochhead A. C. Hereditary coproporphyria. Lancet. 1967 Mar 25;1(7491):632–636. doi: 10.1016/s0140-6736(67)92538-x. [DOI] [PubMed] [Google Scholar]
  15. HUGHES F. B., BRODIE B. B. The mechanism of serotonin and catecholamine uptake by platelets. J Pharmacol Exp Ther. 1959 Oct;127:96–102. [PubMed] [Google Scholar]
  16. Haeger-Aronsen B., Stathers G., Swahn G. Hereditary coproporphyria. Study of a Swedish family. Ann Intern Med. 1968 Aug;69(2):221–227. doi: 10.7326/0003-4819-69-2-221. [DOI] [PubMed] [Google Scholar]
  17. IVERSEN L. L. THE UPTAKE OF NORADRENALINE BY THE ISOLATED PERFUSED RAT HEART. Br J Pharmacol Chemother. 1963 Dec;21:523–537. doi: 10.1111/j.1476-5381.1963.tb02020.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. JARRETT A., RIMINGTON C., WILLOUGHBY D. A. Delta-Aminolaevulic acid and porphyria. Lancet. 1956 Jan 21;270(6908):125–127. doi: 10.1016/s0140-6736(56)91091-1. [DOI] [PubMed] [Google Scholar]
  19. KEZDI P. Neurogenic hypertension in man in porphyria: transient hypertension and tachycardia caused by disruption of the carotid sinus; review of buffer nerve mechanism. AMA Arch Intern Med. 1954 Jul;94(1):122–130. doi: 10.1001/archinte.1954.00250010128010. [DOI] [PubMed] [Google Scholar]
  20. Kramer S., Becker D., Viljoen D. Significance of the porphyrin precursors delta-aminolaevulinic acid (ALA) and porphobilinogen (PBG) in the acute attack of porphyria. S Afr Med J. 1973 Sep 29;47(38):1735–1738. [PubMed] [Google Scholar]
  21. Lomholt J. C., With T. K. Hereditary coproporphyria. A family with unusually few and mild symptoms. Acta Med Scand. 1969 Jul-Aug;186(1-2):83–85. [PubMed] [Google Scholar]
  22. Meyer U. A., Strand L. J., Doss M., Rees A. C., Marver H. S. Intermittent acute porphyria--demonstration of a genetic defect in porphobilinogen metabolism. N Engl J Med. 1972 Jun 15;286(24):1277–1282. doi: 10.1056/NEJM197206152862401. [DOI] [PubMed] [Google Scholar]
  23. Molinoff P. B., Axelrod J. Biochemistry of catecholamines. Annu Rev Biochem. 1971;40:465–500. doi: 10.1146/annurev.bi.40.070171.002341. [DOI] [PubMed] [Google Scholar]
  24. Ridley A. The neuropathy of acute intermittent porphyria. Q J Med. 1969 Jul;38(151):307–333. [PubMed] [Google Scholar]
  25. Sassa S., Granick S., Bickers D. R., Bradlow H. L., Kappas A. A microassay for uroporphyrinogen I synthase, one of three abnormal enzyme activities in acute intermittent porphyria, and its application to the study of the genetics of this disease. Proc Natl Acad Sci U S A. 1974 Mar;71(3):732–736. doi: 10.1073/pnas.71.3.732. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Schley G., Bock K. D., Hocevar V., Merguet P., Rausch-Stroomann J. G., Schröder E., Schümann H. J. Hochdruck und Tachykardie bei der akuten intermittierenden Porphyrie. Klin Wochenschr. 1970 Jan 1;48(1):36–42. doi: 10.1007/BF01486127. [DOI] [PubMed] [Google Scholar]
  27. TEN EYCK F. W., MARTIN W. J., KERNOHAN J. W. Acute porphyria: necropsy studies in nine cases. Proc Staff Meet Mayo Clin. 1961 Aug 16;36:409–422. [PubMed] [Google Scholar]
  28. Thoenen H., Tranzer J. P. Chemical sympathectomy by selective destruction of adrenergic nerve endings with 6-Hydroxydopamine. Naunyn Schmiedebergs Arch Exp Pathol Pharmakol. 1968;261(3):271–288. doi: 10.1007/BF00536990. [DOI] [PubMed] [Google Scholar]
  29. Tschudy D. P., Bonkowsky H. L. Experimental porphyria. Fed Proc. 1972 Jan-Feb;31(1):147–159. [PubMed] [Google Scholar]
  30. Tschudy D. P., Valsamis M., Magnussen C. R. Acute intermittent porphyria: clinical and selected research aspects. Ann Intern Med. 1975 Dec;83(6):851–864. doi: 10.7326/0003-4819-83-6-851. [DOI] [PubMed] [Google Scholar]
  31. Watson C. J. Editorial: Hematin and porphyria. N Engl J Med. 1975 Sep 18;293(12):605–607. doi: 10.1056/NEJM197509182931210. [DOI] [PubMed] [Google Scholar]
  32. Westfall T. C., Brasted M. The mechanism of action of nicotine on adrenergic neurons in the perfused guinea-pig heart. J Pharmacol Exp Ther. 1972 Sep;182(3):409–418. [PubMed] [Google Scholar]
  33. Zieve P. D., Solomon H. M., Krevans J. R. The effect of hematoporphyrin and light on human platelets. I. Morphologic, functional, and biochemical changes. J Cell Physiol. 1966 Apr;67(2):271–279. doi: 10.1002/jcp.1040670207. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES