Dopamine: An Important Neurohormone of the Sympathoadrenal System. Significance of Increased Peripheral Dopamine Release for the Human Stress Response and Hypertension*

Abstract

In human plasma, the concentration of free dopamine (DA) is approximately equal to that of epinephrine (E). Like norepinephrine (NE) and E its concentration may increase during physical effort and stress (Fig. 1). Most of the stress-related increase in plasma DA is derived from peripheral noradrenergic nerve terminals and the adrenal medulla. Because virtually all of the DA is rapidly conjugated upon release, it is necessary to measure plasma total (free + conjugated) DA. When dietary sources are controlled, the total DA concentration can be used as an indicator of the intensity of the sympathetic response and possibly the level of training in animals and humans. In normal individuals, plasma DA and blood pressure (BP) are usually negatively correlated since during a low level sympathetic discharge the hypotensive action of DA via dopaminergic vascular receptors predominates. The DA action on BP is, however, biphasic and dependent on its concentration. In many hypertensive patients, hypertensive peaks, which cannot be accounted for by rises in NE and E, are associated with very large stimulus-elicited increases in total DA into a range in which its hypertensive action via beta and alpha-receptors could temporarily predominate. Alternatively, this rise in DA could be a marker of the sympathetic discharge or a negative modulator of other hypertensive influences rather than the cause of the elevated BP. In primary aldosteronism, there is a more sustained increase in circulating DA. In both groups of patients the DA levels decrease with successful treatment. Concentrations of total DA and of free + conjugated NE + E in plasma are a more sensitive measure of sympathetic activity than are levels of free catecholamines, and they may provide a clinically useful biochemical index for categorizing hypertension and following its treatment.

Dopamine Selectively Induces Migration and Homing of Naive CD8+ T Cells via Dopamine Receptor D3

“…In the periphery, dopamine is primarily the precursor of norepinephrine and epinephrine, the major neurotransmitter of the sympathetic nerve system, and the major adrenomedullary hormone, respectively. Dopamine is also released from the sympathetic nerve endings and may function as a neurohormone (2). In particular, dopamine is known to directly control the functions of kidney and vasculature by affecting Na ϩ homeostatis, hormone secretion, renal blood flow, and cardiovascular function (1,3).…”

“…In particular, dopamine is known to directly control the functions of kidney and vasculature by affecting Na ϩ homeostatis, hormone secretion, renal blood flow, and cardiovascular function (1,3). Furthermore, plasma contains a significant level of dopamine, most of which is conjugated to sulfate or glucuronide (2). Five types of dopamine receptors have been identified to date and termed D1, 3 D2, D3, D4, and D5 (1,4).…”

Association of High Levels of Plasma Free Dopamine With Future Coronary Events in Patients With Coronary Artery Disease

“…Dopamine is secreted from sympathetic nerve endings and the adrenal gland 7 and then rapidly inactivated by conversion to a conjugated form in plasma. 7,17 Because circulating dopamine is present almost entirely (>98%) in the conjugated form, 7,9 plasma levels of free dopamine (ie, biologically active dopamine) are mainly determined by the net balance between its conjugation and deconjugation by phenol sulfotransferase and arylsulfatase, respectively.…”

“…7,17 Because circulating dopamine is present almost entirely (>98%) in the conjugated form, 7,9 plasma levels of free dopamine (ie, biologically active dopamine) are mainly determined by the net balance between its conjugation and deconjugation by phenol sulfotransferase and arylsulfatase, respectively. 9,[18][19][20] Although the precise regulatory mechanisms for the activity of these enzymes remain unclear, the deconjugation of conjugated dopamine to free dopamine is known to increase in patients with chronic heart failure, 21 in whom sympathetic activation occurs chronically.…”

“…Peripheral circulating dopamine is derived from 2 main sources: the sympathetic nerves and the adrenal medulla. 7 Plasma levels of endogenous dopamine are increased in patients with congestive heart failure 8 and in other circumstances in which the sympathoadrenal system is stimulated, such as upright posture, physical exercise stress, and hypoglycemia. 9 However, it is unclear whether plasma levels of free endogenous dopamine may have a predictive value for future cardiovascular events in patients with coronary artery disease (CAD).…”