Dopamine modulates von Willebrand factor secretion in endothelial cells via D2–D4 receptors

Abstract

Summary. Objective: von Willebrand factor (VWF) is acutely released from endothelial cells in response to numerous calcium-raising agents (e.g. thrombin, histamine) and cAMPraising agents (e.g. epinephrine, adenosine, vasopressin). In contrast, very few inhibitors of endothelial VWF secretion have been described. The neurotransmitter dopamine is a modulator of exocytosis in several endocrine cells, and is possibly involved in the regulation of several endothelial cell functions. We therefore investigated the effect of dopamine on endothelial VWF secretion. Results: Dopamine, D2/D3-and D4-specific agonists inhibited histamine-but not thrombin-induced VWF secretion. Expression of dopamine D2, D3 and D4 receptors was demonstrated by reverse transcription polymerase chain reaction (RT-PCR) in both human aortic (HAEC) and umbilical vein (HUVEC) endothelial cells. D2-D4 agonists did not inhibit histamine-induced rise in [Ca 2+ ] i : they inhibited histamine-induced secretion even in the absence of extracellular calcium. Thus, the dopamine effects are not mediated by [Ca 2+ ] i -dependent signalling. D2/D3-and D4-specific agonists inhibited neither the rise in cAMP nor VWF secretion in response to epinephrine and adenosine, arguing against an effect on cAMP-mediated signalling. D1 and D5 receptors were not detected in HAEC or HUVEC by RT-PCR, and the D1/ D5-specific agonist SKF 38 393 failed to modulate VWF secretion, arguing against a role for these receptors in endothelial exocytosis. Conclusions: Dopamine inhibits histamine-induced endothelial exocytosis by activating D2-D4 receptor, via a mechanism distinct from [Ca 2+ ] i -or cAMPmediated signaling. In contrast, D1 and D5 receptors are not functionally expressed in cultured endothelial cells. Dopamine agonists may be useful as inhibitors of endothelial activation in inflammation and cardiovascular disease.

Association Between Antipsychotic Use and Risk of Acute Myocardial Infarction

“…[33][34][35][36][37][38] Additionally, there are several blood coagulation pathways involving D 3 receptors systems, including the activation of platelet aggregation and the secretion of the procoagulant von Willebrand factor. 39,40 Hence, D 3 receptors blockade could also predispose the patient to the formation of acute thrombosis in stenotic coronary arteries, contributing to AMI.…”

Cushing's disease and hypertension: in vivo and in vitro study of the role of the renin-angiotensin-aldosterone system and effects of medical therapy

“…After 80 days of medical combination therapy, biochemical remission was achieved in almost 90% of the patients, which was accompanied by a significant decrease in both systolic and diastolic blood pressure (13). Although the decrease in blood pressure might be a direct consequence of decreased cortisol levels, both somatostatin receptors and dopamine receptors have been reported to be present in endothelial cells (14,15). Therefore, pasireotide and cabergoline may directly affect vascular tone.…”

Dopamine D1-Like Receptors Suppress the Proliferation of Macrophages Induced by Ox-LDL

“…It was shown that both the D 1 and D 5 receptors were present in macrophages, as determined by immunohistochemistry, immunoblotting and RT-PCR, using human umbilical vein endothelial cells (HUVEC, ATCC, Manassas, VA) as a negative control [24] and the embryonic thoracic aortic smooth muscle cells from normotensive Berlin-Druckrey IX rats (A10, ATCC, Manassas, VA) as a positive control [12,13] (Fig. 1A-1C).…”