Homeostasis of Dopamine
Nira Ben-Jonathan in Dopamine, 2020
This chapter provides an overview of the fundamental processes that govern dopamine (DA) homeostasis: synthesis, metabolism, release, reuptake, and storage. At any given time, DA homeostasis is determined by multiple complementary processes that are tightly regulated and well-coordinated. Catecholamine biosynthesis involves several sequential enzymatic reactions, with tyrosine hydroxylase (TH) serving as the rate-limiting step. Metabolic degradation is carried out primarily by monoamine oxidase (MAO) and catechol-O-methyl transferase (COMT), with additional glucuronidation and sulfation reactions. Within the producing cells, DA is stored in secretory vesicles whose main function is to protect it from degradation and enable its regulated release by a calcium-dependent exocytosis. Several types of transporters-the dopamine transporter (DAT), the vesicular monoamine transporters (VMATs), and organic cation transporters (OCTs)-are involved with the termination of the action of released DA through reuptake mechanisms and repackaging into the secretory granules. The different cytoarchitecture of DA within the "closed system" of the brain and the "open system" of the periphery necessitates several modifications of the fundamental processes of synthesis, metabolism, storage, transport and release of peripheral DA.
Sources Of Dopamine In Peripheral Tissues
M.D. Francesco Amenta in Peripheral Dopamine Pathophysiology, 2019
The existence of a dopaminergic peripheral system was progressively determined by contribution of physiological, biochemical, and morphological investigations. It is well known that dopamine formation is a step of catecholamine synthesis. Direct evidence of dopaminergic neurons in the periphery has been obtained for only a few tissues. A. Bjorklund and co-workers in 1970 demonstrated that the predominant catecholamine in rat sympathetic ganglia is dopamine. Less is known about peripheral dopaminergic neurons from autonomic ganglia. The existence of a dopaminergic innervation causing vasodilatation in the kidney was first demonstrated by C. Bell and W. J. Lang in 1973. One peripheral source of dopamine has been recently identified in the urogenital system. Dopaminergic receptors are present through the whole cardiovascular system, but a widespread dopaminergic innervation of heart and vessels is to be defined. These receptors on the parathyroid cell membrane activate adenylate cyclase and cause parathyroid hormone secretion.
Treatment and its Effectiveness in Relapse Prevention Associated with Crack Cocaine
Andrew McBride in Substance Misuse in Primary Care, 2018
One of the biggest barriers to treatment for crack cocaine users has been the undeniably strong stereotypes associated with crack use. These stereotypes are most commonly rooted in historical racism, attitudes to poverty and the fear that these issues bring when associated with inaccurate and sensationalist reporting by the media. Crack cocaine is a different drug when compared to opiates and services need to acknowledge that national policies and practice have predominately reflected the needs of opiate users leading to imbalances in provision within generic treatment providers. The 'high' experienced by a person taking crack or cocaine is produced by a chemical called dopamine. The combination of increased adrenaline levels and low dopamine levels after a period of using can produce the feelings of being 'wired' or 'prang'. Crack cocaine use can be associated with high levels of health complaints, drug related deaths and also an increase in criminal involvement.
Auxiliary role of D5 dopamine receptor as a marker in paranoid schizophrenia patients
Published in Psychiatry and Clinical Psychopharmacology, 2019
Mahkameh Soleiman Meygooni, Mohammad Amin Minaei Asil, Geghani Taroyan Haftvani, Firouzeh Morshedzadeh, Davood Zaeifi
OBJECTIVE: Schizophrenia, commonly develops in adolescents and young adults and Paranoid is the most common type. Newly progress in molecular biology and imaging techniques has enabled new insight into schizophrenia research. Recent research reveals the key roles of D3, D4 and D5 dopamine receptor in presenting types of schizophrenia, particularly the paranoid. The purpose of this study was to the evaluation of D5 along with D3 dopamine receptor expression in schizophrenia patients. METHOD: 96 venous blood from 51 drug-free, 15 naive and 30 healthy were prepared and their expression level of mRNA for D3 and D5 dopamine receptor were investigated based on β-actin expression as housekeeping gene. RESULTS: D3 expressed about 33.3%, 73.3% and 27.4% in healthy, naive and drug-free patients respectively, but D5 just expressed in 86.6% of healthy samples and none of the patients were expressed D5. CONCLUSION: Expression frequency of D3 and D5 dopamine receptor reveals significant differences between naïve and drug-free patient against healthy individuals. D3 and D5, both have the possible potential for almost more accurate diagnosis usage, and the severity of the disease could be related to the D5 dopamine receptor.
A review of adverse events linked to dopamine agonists in the treatment of Parkinson’s disease
Published in Expert Opinion on Drug Safety, 2016
Roberto Ceravolo, Carlo Rossi, Eleonora Del Prete, Ubaldo Bonuccelli
Introduction: Dopamine agonists are highly effective as adjunctive therapy to levodopa in advanced Parkinson’s disease. These drugs have rapidly gained popularity as a monotherapy in the early stages of Parkinson’s disease for patients less than 65–70 years old since they are about as effective as levodopa but patients demonstrate a lower tendency to develop motor complications. However, dopamine agonists could have peripheral and central side-effects which are often the reason for the discontinuation of the treatment. Areas covered: This article presents an overview of the efficacy and the potential negative effects related to the use of dopamine agonists in the treatment of Parkinson’s disease. Expert opinion: Beyond the new generation non ergot dopamine agonists, no strong evidences allow the choice of a specific dopamine agonists for Parkinson ‘s disease treatment and by now dopamine agonists treatment should be tailored on specific adverse events profile.
VMAT2 and Parkinson’s disease: harnessing the dopamine vesicle
Published in Expert Review of Neurotherapeutics, 2014
Despite a movement away from dopamine-focused Parkinson’s disease (PD) research, a recent surge of evidence now suggests that altered vesicular storage of dopamine may contribute to the demise of the nigral neurons in this disease. Human studies demonstrate that the vesicular monoamine transporter 2 (VMAT2; SLC18A2) is dysfunctional in PD brain. Moreover, studies with transgenic mice suggest that there is an untapped reserve capacity of the dopamine vesicle that could be unbridled by increasing VMAT2 function. Therapeutic manipulation of VMAT2 level or function has the potential to improve efficacy of dopamine derived from administered levodopa, increase dopamine neurotransmission from remaining midbrain dopamine neurons and protect against neurotoxic insults. Thus, the development of drugs to enhance the storage of release of dopamine may be a fruitful avenue of research for PD.
Related Knowledge Centers
- Neurotransmitters
- Tyrosine
- Epinephrine
- Norepinephrine
- Biogenic Monoamines
- Dopamine Receptors
- Catecholamines