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Dopamine in the Immune and Hematopoietic Systems
Published in Nira Ben-Jonathan, Dopamine, 2020
The complete dopaminergic system, including biosynthetic and metabolizing enzymes, transporters and receptors, is present in almost all cells that are derived from lymphoid and myeloid lineages. DA is involved in a number of neurological and psychiatric disorders, as well as in several autoimmune diseases. Altered expression of DAR in peripheral lymphocytes from patients with SLE, MS, and RA supports the importance of DA regulations in autoimmunity. In some autoimmune diseases, T cells seem to have abnormal DAR expression, DA production, and/or altered responsiveness to DA. Multiple DA-altering drugs such as L-Dopa, bromocriptine, haloperidol, quinpirole, pergolide, pimozide, amantadine, tetrabenazine, and butaclamol had variable beneficial effects in these diseases. The DA-induced activation of resting Teffs and suppression of Tregs could be useful in cancer immunotherapy and infectious diseases, while the suppression of certain DAR in autoimmune diseases, pro-inflammatory, and cancerous T cells, could be advantageous. Endothelial cells, which play critical roles in vascular biology and angiogenesis, also can synthesize and release DA and variably express all DAR.
Dopamine Receptor Studies with Positron Emission Tomography
Published in W. R. Wayne Martin, Functional Imaging in Movement Disorders, 2019
Several points regarding the nonsteady-state method need emphasis. First, it is assumed that nonspecific binding in the cerebellum is the same as in the striatum. Implicit in this assumption is that no specific binding occurs in cerebellum. Logan et al.36 show that stereoselective blocking with (+) butaclamol (which blocks D2 dopaminergic receptors) reduces the uptake of 18F-spiperone in cerebellum and suggest that this indicates the presence of saturable binding sites. It is important to note that the difference was demonstrable only at relatively late times after injection. The impact of the resulting error in the estimate of nonspecific binding (actually the estimate of the free fraction in compartment 2, f2), results in a modest error in the estimate of the combined forward rate constant (the product of ka and Bmax).47 From a practical point of view, the greatest disadvantage of using the nonsteadystate method with 18F-spiperone is the length of time required for the study, at least 2 to 3 h after radioligand injection.36,37,47 Hopefully, a ligand with faster kinetics (i.e., rapid association and reversibility), such as raclopride, would permit a much shorter study.42
Prejunctional Dopamine Receptor Stimulants
Published in M.D. Francesco Amenta, Peripheral Dopamine Pathophysiology, 2019
The question as to whether or not bromocriptine stimulates DA1 receptors remains controversial. Positive evidence has been obtained in isolated, precontracted vessels, i.e., dose-dependent relaxation of mesenteric and middle cerebral arteries of the rabbit, and dilation of vessels in the perfused, denervated rat kidney occur within the same concentration range as that required to produce comparable effects with dopamine. The vasorelaxant effects of both agonists are attenuated by a variety of DA receptor antagonists ([ + ] butaclamol, droperidol, metoclopramide, haloperidol, ergometrine, apomorphine), whereas (-) butaclamol and β-adrenoceptor antagonists are ineffective.62-66 Such findings are, however, difficult to reconcile with the compound’s lack of stimulant activity on DA-sensitive adenylate cyclase in homogenates of bovine retina and rat striatum. In both tissues, it acts only as a competitive antagonist of the effects of DA.16,67
Effect of subchronic exposure to ambient fine and ultrafine particles on rat motor activity and ex vivo striatal dopaminergic transmission
Published in Inhalation Toxicology, 2023
María-de-los-Angeles Andrade-Oliva, Yazmín Debray-García, Guadalupe-Elide Morales-Figueroa, Juan Escamilla-Sánchez, Omar Amador-Muñoz, Raúl V. Díaz-Godoy, Michael Kleinman, Benjamín Florán, José-Antonio Arias-Montaño, Andrea De Vizcaya-Ruiz
For the competition assay, membranes (one preparation per animal) were incubated for 90 min at 25 °C in incubation buffer containing 2 nM [3H]-spiperone and increasing concentrations of dopamine (eight concentrations, 10−9 to 10−4 M, triplicate determinations). Non-specific binding was determined in the presence of 100 nM (±)-butaclamol. The incubation buffer was supplemented with 100 nM ketanserin (to prevent [3H]-spiperone from binding to 5-HT2 receptors) and 10 μM pargyline/200 μM ascorbic acid to prevent dopamine degradation. Incubations were terminated by rapid filtration through GF/B filters presoaked in 0.3% polyethylenimine for 2 h. Filters were soaked in 3 ml of scintillation liquid, and the tritium content was determined by scintillation counting. The protein content was determined by a bicinchoninic acid assay (BCA; Pierce, Rockford, IL, USA) with BSA as a standard.