Plasma Free Dopamine: Physiological Variability and Pathophysiological Significance

Abstract

Dopamine (DA) is the most abundant catecholamines in human plasma and exists mostly in the sulfoconjugated form (DA sulfate), a biologically inactive metabolite. The paucity of unconjugated DA (PDA) in plasma throws doubt on its physiological significance. However, PDA, when measured with a highly sensitive radioenzymatic method, showed quite different features from norepinephrine and epinephrine in some types of clinical hypertension, lower in essential hypertension and higher in primary aldosteronism and pheochromocytoma. There was a weak but significant correlation between the values of PDA and DA sulfate measured in the same specimens, but DA sulfate was more susceptible to impaired renal function. Upright posture, high salt diets and an intravenous injection of metoclopramide (MCP, 10 mg), a DA receptor antagonist, induced a slight but significant increase in PDA in normal and hypertensive subjects. An intravenous dexamethasone (2 mg) caused a gradual increase in PDA over 150 min after medication, which was completely blocked by concomitant administration of a-methyl p-tyrosine, a tyrosine hydroxylase inhibitor. The responses of PDA to both high salt diets and MCP were blunted in salt-sensitive patients with uncomplicated essential hypertension. The results suggest that DA is not only a precursor of norepinephrine biosynthesis but also plays an inherent role as an active neurotransmitter in the peripheral sympathoadrenal system, and that PDA is a sensitive marker of peripheral dopaminergic activity, which may operate to modulate the cardiovascular and endocrine functions and participate in the pathogenesis of some types of hypertension. (Hypertens Res 1995; 18 Suppl. I: S65-S72)

Peripheral dopamine in hypertension and associated conditions

“…The possibility that DA sulfate represents a reserve pool of free DA released by concomitant glucocorticoid increase-associated stress is supported by the findings that glucocorticoids increase free DA in man. [33][34][35] This may be due either to cortisol-induced stimulation of tyrosine hydroxylase 35 the crucial catecholamines synthesising enzyme or of sulfatase activity 36 releasing free DA from DA sulfate, When administering dexamethasone to healthy subjects we have observed 37 a decreased degree of conjugation of DA from 94 ± 2% to 81 ± 6%, P Ͻ 0.05 and NA from 89 ± 2% to 61 ± 9%, P Ͻ 0.01. It is conceivable that an alternative source of free DA would be operative only in the case of considerable cortisol increase-associated stress while moderate homeostatic adjustment to posture and high salt intake 34 could be accommodated by an increased DA synthesis and release.…”

“…75 Dopamine excess originating in neoplastic tissues includes dopamine-producing pheochromocytoma which carries less than previously suspected the connotation of malignity. 80 Hypersecretion of DA can usually be detected by elevated plasma free DA 34 and DA sulfate. 34,68 The hyperdopaminergic condition, in which outpouring of DA from the tumor overwhelms the patient's ability to conjugate, 81 is usually reflected by normo-or hypotension.…”

“…80 Hypersecretion of DA can usually be detected by elevated plasma free DA 34 and DA sulfate. 34,68 The hyperdopaminergic condition, in which outpouring of DA from the tumor overwhelms the patient's ability to conjugate, 81 is usually reflected by normo-or hypotension. It rarely results in an increased outlet resistance of the prostatic urethra reversible after partial excision of the tumor and decreased DA concentration.…”

“…Radioenzymatic determination 9,34 is preferable to the less sensitive HPLC techniques. Plasma DA sulfate under controlled conditions is at present a surrogate even if imperfect DA marker substituting for low plasma free DA detectability.…”

Exercise-Induced Norepinephrine Decreases Circulating Hematopoietic Stem and Progenitor Cell Colony-Forming Capacity

“…Although it is known that NE increases after exercise [25], an effect on hematopoietic progenitor cell proliferative capacity remains elusive. We are the first to analyze the biologically active form [26] of free (unconjugated) NE, which is probably more relevant for an influence on CPC functionality. Benschop et al [27] and Dar et al [28] showed that increased catecholamines lead to elevated leucocytes and hematopoietic stem and progenitor cells (HSPCs) in peripheral blood.…”