This Article Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by GOLDSTEIN, D. S. Articles by FOLIO, C. J. Search for Related Content PubMed PubMed Citation Articles by GOLDSTEIN, D. S. Articles by FOLIO, C. J.

Neuronal Source of Plasma Dihydroxyphenylalanine

Hypertension-Endocrine Branch, National Heart, Lung, and Blood Institute Bethesda, Maryland 20892
The Developmental Endocrinology Branch, National Institute of Child Health and Human Development Bethesda, Maryland 20892
The Intramural Research Program, National Institute of Neurological and Communicative Disorders and Stroke, National Institutes of Health Bethesda, Maryland 20892

Address requests for reprints to: Dr. David Goldstein, Building 10, Room 8C118, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892.

The source and significance of plasma levels of dihydroxyphenylalanine (DOPA), the precursor of the endoge-nous catecholamines, have been unknown. We measured arterial and venous plasma DOPA concentrations in healthy subjects at rest, patients who had undergone regional sympathectomies or were undergoing general anesthesia, and subjects during procedures (tilt, oral clonidine, or iv isoproterenol, yohimbine, tri-methaphan, or diazepam) known to affect plasma norepineph-rine levels. We also measured plasma DOPA in laboratory animals during anesthesia, after adrenalectomy, or after administration of -methyl-para-tyrosine, which competitively inhibits tyrosine hydroxylase, the intraneuronal enzyme catalyzing the rate-limiting step in catecholamine biosynthesis. In virtually all healthy subjects there was an arteriovenous increment in plasma DOPA (mean increase, 32%; P < 0.001), whereas in sympathectomized patients there was not (mean decrease, 16%; P < 0.001 compared with healthy subjects). Except for small decreases after clonidine treatment, none of the above procedures affected plasma DOPA levels. Plasma DOPA decreased during general anesthesia and returned to baseline upon reversal of the anesthesia. Adrenalectomy had no effect on plasma DOPA. -Methyl-para-tyrosine decreased plasma DOPA by 62% (P < 0.01). The results support the suggestion that DOPA can pass across sympathetic neuronal membranes to reach the general circulation. If so, then the regional rate of appearance of DOPA in plasma may be related to the regional rate of tyrosine hydroxylation. Conversely, DOPA taken up from the circulation may provide a source for catecholamine biosynthesis in tissues devoid of tyrosine hydroxylase.

Received September 24, 1986.

This article has been cited by other articles:

				N. R. Keller, A. Diedrich, M. Appalsamy, S. Tuntrakool, S. Lonce, C. Finney, M. G. Caron, and D. Robertson Norepinephrine Transporter-Deficient Mice Exhibit Excessive Tachycardia and Elevated Blood Pressure With Wakefulness and Activity Circulation, September 7, 2004; 110(10): 1191 - 1196. [Abstract] [Full Text] [PDF]

				D. S. Goldstein, G. Eisenhofer, and I. J. Kopin Sources and Significance of Plasma Levels of Catechols and Their Metabolites in Humans J. Pharmacol. Exp. Ther., June 1, 2003; 305(3): 800 - 811. [Abstract] [Full Text] [PDF]

				D. S. Goldstein, D. Robertson, M. Esler, S. E. Straus, and G. Eisenhofer Dysautonomias: Clinical Disorders of the Autonomic Nervous System Ann Intern Med, November 5, 2002; 137(9): 753 - 763. [Abstract] [Full Text] [PDF]

				D. S. Goldstein, C. Holmes, S.-T. Li, S. Bruce, L. V. Metman, and R. O. Cannon III Cardiac Sympathetic Denervation in Parkinson Disease Ann Intern Med, September 5, 2000; 133(5): 338 - 347. [Abstract] [Full Text] [PDF]

				D. S. Goldstein, K. J. Swoboda, J. M. Miles, S. W. Coppack, A. Aneman, C. Holmes, I. Lamensdorf, and G. Eisenhofer Sources and Physiological Significance of Plasma Dopamine Sulfate J. Clin. Endocrinol. Metab., July 1, 1999; 84(7): 2523 - 2531. [Abstract] [Full Text]

				G. Eisenhofer, B. Rundqvist, and P. Friberg Determinants of cardiac tyrosine hydroxylase activity during exercise-induced sympathetic activation in humans Am J Physiol Regulatory Integrative Comp Physiol, March 1, 1998; 274(3): R626 - R634. [Abstract] [Full Text] [PDF]

				M. Linnoila, J. Oliver, B. Adinoff, and W. Z. Potter High Correlations of Norepinephrine, Dopamine, and Epinephrine and Their Major Metabolite Excretion Rates Arch Gen Psychiatry, August 1, 1988; 45(8): 701 - 704. [Abstract] [PDF]