CHARACTERIZATION OF DOPAMINERGIC RECEPTORS IN HUMAN UMBILICAL CORD VESSELS
Creators: name: Castro, Weverton
name: De Nucci, Gilberto
Publisher: name: figshare
Year: 2022
Subjects: subject: 119999 Medical and Health Sciences not elsewhere classified
subject: FOS: Other medical sciences
subject: Pharmacology
subject: 111503 Clinical Pharmacy and Pharmacy Practice
subject: FOS: Clinical medicine
subject: 111504 Pharmaceutical Sciences
subject: 111599 Pharmacology and Pharmaceutical Sciences not elsewhere classified
subject: Neuroscience
subject: 110201 Cardiology (incl. Cardiovascular Diseases)
subject: Cardiology
subject: 110299 Cardiorespiratory Medicine and Haematology not elsewhere classified
subject: 170106 Health, Clinical and Counselling Psychology
subject: FOS: Psychology
subject: Neuroscience and Physiological Psychology
subject: Structural Biology
subject: Molecular Biology
subject: 110899 Medical Microbiology not elsewhere classified
subject: FOS: Health sciences
subject: 60110 Receptors and Membrane Biology
subject: FOS: Biological sciences
subject: 60112 Structural Biology (incl. Macromolecular Modelling)
subject: Cell Biology
subject: 60113 Synthetic Biology

description: There is a high expression of dopaminergic receptors in the central nervous system represented by the D1-like (D1 and D5) and D2-like (D2, D3, D4) subfamily. Activation of D1-like receptors increases the production of the second messenger 3'5'-adenosine-cyclic-monophosphate (cAMP), on the other hand, the activation of D2-like leads to its decrease. The synthesis of dopamine in vessels is not yet clear in the literature, however, it is has known that tyrosine hydroxylase (TH) and dopa-decarboxylase in the tunic medium is stored in human umbilical cord vessel endothelia (HUCV) in both artery and vein. Endothelial cells present in the smooth muscle of vessels are responsible for the synthesis of vasodilator and vasoconstrictor mediators that modulate vascular reactivity. Considering the endothelial production of catecholamines in the human umbilical cord as well as the release of dopamine and nitric oxide which is shown to be able to nitrate dopamine to 6-nitrodopamine (6-ND), the study aims to elucidate the role of 6-ND in HUCV rings. The study included normotensive women aged over 18 years and under 42, who go through natural childbirth or cesarean delivery in the maternity hospital from Campinas-SP, in which 96 umbilical cords were collected, and the Informed Consent (TCL) was given. Rings of about 3 mm of HUA and HUV were extracted and suspended in an organ bath under isometric tension, followed by the administration of 6-ND and other pharmacological media. In tissues in which the endothelium was maintained, the release of 6-ND was reduced by performing a pre-treatment with L-NAME at 100 µM. In the presence of 6-ND, NG-monomethyl-L-arginine (L-ANME) or soluble guanylyl cyclase (ODQ) heme site, noradrenaline and epinephrine did not contract HUC. However, the 6-ND, at 10 µM produced a significant shift (p&lt;0.05) to the right of the dopamine concentration curves in both vessels (pEC50 HUA 4.2 ± 0.1; pEC50 HUV: 4, 2 ± 0.1 mN; n = 5/8). In the concentration-response curve of sumanirole (D2-like agonist) when incubating 6-ND at 1 uM there was a shift to the right (Emax HUA 13.0 ± 3.6, mN; Emax HUV 13.8 ± 2.7 n = 4/8). However, in relaxation with haloperidol (D2-like antagonist) after a pre-contraction with 10nM U-46619 there was a concentration-dependent relaxation in HUA with preserved endothelium (pEC50 8.0 ± 0.1 mN; Emax 85.4 ± 5.9%; n = 5/9) and HUV (pEC50 7.6 ± 0.1; Emax 62.1 ± 7.6%; n = 4/8). Incubation with the 10 nM D1-like receptor antagonist SCH-23390 abolished the relaxation with fenoldopam in HUA and HUV, and did not affect those induced by 6-ND. Consequently, the release of 6-ND has been inhibited by the removal of the endothelium or by pre-treatment of vessels with the NO synthesis inhibitor L-NAME, which shows that 6-ND synthesis is coupled to NO and its mechanisms are involved in relaxation induced by dopamine. 6-ND antagonizes D2-like receptors present in the vasculature of the HUCV.