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European Journal of Pharmacology Aug 2022Dopamine levels in the central nervous system change under pathological conditions such as Parkinson's disease, Huntington's disease, and addiction. Under those...
Dopamine levels in the central nervous system change under pathological conditions such as Parkinson's disease, Huntington's disease, and addiction. Under those pathological conditions, astrocytes become reactive astrocytes characterized by morphological changes and the release of inflammatory cytokines involved in pathogenesis. However, it remains unclear whether dopamine regulates astrocytic morphology and functions. Elucidating these issues will help us to understand the pathogenesis of neurodegenerative diseases caused by abnormal dopamine signaling. In this study, we investigated the effects of dopamine on IL-6 expression and process formation in rat primary cultured astrocytes and acute hippocampal slices. Dopamine increased IL-6 expression in a concentration-dependent manner, and this was accompanied by CREB phosphorylation. The effects of a low dopamine concentration (1 μM) were inhibited by a D1-like receptor antagonist, whereas the effects of a high dopamine concentration (100 μM) were inhibited by a β-antagonist and enhanced by a D2-like receptor antagonist. Furthermore, dopamine (100 μM) promoted process formation, which was inhibited by a β-antagonist and enhanced by both an α-antagonist and a D2-like receptor antagonist. In acute hippocampal slices, both a D1-like receptor agonist and β-agonist changed astrocytic morphology. Together, these results indicate that dopamine promotes IL-6 expression and process formation via D1-like receptors and β-adrenoceptors. Furthermore, bidirectional regulation exists; namely, the effects of D1-like receptors and β-adrenoceptors were negatively regulated by D2-like receptors and α-adrenoceptors.
Topics: Animals; Astrocytes; Dopamine; Dopamine Agonists; Interleukin-6; Rats; Receptors, Adrenergic; Receptors, Adrenergic, alpha-2; Receptors, Dopamine D1; Receptors, Dopamine D2
PubMed: 35738452
DOI: 10.1016/j.ejphar.2022.175110 -
Free Radical Biology & Medicine Jun 2023Acute lung injury (ALI) or its severe form, acute respiratory distress syndrome (ARDS) is a life-threatening illness without effective therapeutic interventions...
Acute lung injury (ALI) or its severe form, acute respiratory distress syndrome (ARDS) is a life-threatening illness without effective therapeutic interventions currently. Multiple lines of evidence indicated that overwhelming inflammatory responses and impaired epithelial barrier contributed to the pathogenesis of ALI/ARDS. Recently, dopamine (DA) system was identified to participate in various pulmonary diseases. Here, we discovered that dopamine D1-like receptors mainly expressed in macrophages and airway epithelial cells (AECs), which were downregulated by lipopolysaccharide (LPS) challenge in ALI mouse lung. SKF38393 (SKF) is a selective agonist for D1-like receptors and was demonstrated to inhibit excessive inflammatory responses and oxidative stress in THP-1 cell-derived macrophages and Beas-2B cells, as well as improve airway epithelial barrier dysfunction induced by LPS stimulation. Moreover, SKF administration could effectively decrease pulmonary inflammation, ameliorate tissue damage in the LPS-triggered ALI mice. The broad protective actions of SKF might be attributed to the activation of Nrf2 antioxidative system by use of the specific inhibitor, ML385. This study offers evidence of potent immunoregulatory activity of SKF in macrophages, AECs as well as ALI mouse model, which opens novel therapeutic avenues for the intervention of ALI/ARDS.
Topics: Animals; Mice; Lipopolysaccharides; Dopamine Agonists; Dopamine; Acute Lung Injury; Macrophages; Epithelial Cells; Respiratory Distress Syndrome; Receptors, Dopamine D1; Lung
PubMed: 36965538
DOI: 10.1016/j.freeradbiomed.2023.03.016 -
European Journal of Neurology Feb 2024Impulse control disorders (ICDs) are common among Parkinson's disease patients using dopamine agonists. We wanted to determine whether ICD patients have higher dopamine...
BACKGROUND AND PURPOSE
Impulse control disorders (ICDs) are common among Parkinson's disease patients using dopamine agonists. We wanted to determine whether ICD patients have higher dopamine agonist serum concentrations than those without any sign of ICD.
METHODS
Patients who used either pramipexole or ropinirole depot once daily were screened for ICDs using the validated Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale. Those who scored above the cut-off for one or more of the four defined ICDs (gambling, compulsive sexual behavior, compulsive shopping, and binge-eating) were compared in a case-control study to patients who scored zero points (no evidence of ICD) on the same items. They were examined clinically and evaluated using relevant scales. Three blood samples were taken on the same day: before daily dose, and then 6 and 12 h later.
RESULTS
Forty-six patients were included: 19 ICD-positive and 27 controls. Ropinirole serum concentrations 6 h after daily intake (C ) were higher in the case group compared to the control group, as was the daily ropinirole dosage. No differences were observed in serum concentrations, dosage or total drug exposure for pramipexole. Disease duration and length of dopamine agonist treatment was significantly longer among ICD patients for ropinirole, but not for pramipexole.
CONCLUSIONS
The use of pramipexole may in itself confer high ICD risk, whereas ICDs among ropinirole users depend more on serum concentration and drug exposure. The pharmacokinetic properties of ropinirole make it challenging to predict its effects on patients, which supports the need for therapeutic drug monitoring to reduce risk of ICD.
Topics: Humans; Dopamine Agonists; Parkinson Disease; Pramipexole; Case-Control Studies; Disruptive, Impulse Control, and Conduct Disorders
PubMed: 37955562
DOI: 10.1111/ene.16144 -
Pituitary Feb 2020Consensus guidelines recommend dopamine agonists (DAs) as the mainstay treatment for prolactinomas. In most patients, DAs achieve tumor shrinkage and normoprolactinemia... (Review)
Review
Consensus guidelines recommend dopamine agonists (DAs) as the mainstay treatment for prolactinomas. In most patients, DAs achieve tumor shrinkage and normoprolactinemia at well tolerated doses. However, primary or, less often, secondary resistance to DAs may be also encountered representing challenging clinical scenarios. This is particularly true for aggressive prolactinomas in which surgery and radiotherapy may not achieve tumor control. In these cases, alternative medical treatments have been considered but data on their efficacy should be interpreted within the constraints of publication bias and of lack of relevant clinical trials. The limited reports on somatostatin analogues have shown conflicting results, but cases with optimal outcomes have been documented. Data on estrogen modulators and metformin are scarce and their usefulness remains to be evaluated. In many aggressive lactotroph tumors, temozolomide has demonstrated optimal outcomes, whereas for other cytotoxic agents, tyrosine kinase inhibitors and for inhibitors of mammalian target of rapamycin (mTOR), higher quality evidence is needed. Finally, promising preliminary results from in vitro and animal reports need to be further assessed and, if appropriate, translated in human studies.
Topics: Cabergoline; Dopamine Agonists; Female; Humans; Male; Prolactinoma
PubMed: 31522358
DOI: 10.1007/s11102-019-00987-3 -
Pituitary Oct 2023Giant prolactinomas are a rare entity, representing approximately 5% of all prolactinomas. A systematic review of 196 adult cases was performed. A comparison of the... (Review)
Review
PURPOSE
Giant prolactinomas are a rare entity, representing approximately 5% of all prolactinomas. A systematic review of 196 adult cases was performed. A comparison of the clinical, biochemical and radiological characteristics, management and therapeutic outcomes in men versus women is made.
METHODS
A structured search was conducted using the term 'giant prolactinoma'. Following inclusion criteria were used: diameter ≥ 40 mm, prolactin levels > 1000 ng/ml and no concomitant GH/ ACTH secretion.
RESULTS
196 cases were included [age: 38 (28-50) years, F/M ratio: 1/3.6]. Median tumor diameter was 53 (43-69) mm. Pituitary deficiency was present in 91% of cases, with hypogonadotropic hypogonadism being the most frequent. Most common presenting symptoms were visual impairment (73%) and headache (50%) in men and amenorrhea (58%) in women. 82% of cases were treated with a dopamine agonist (DA) as first-line treatment which led to normoprolactinemia, tumor shrinkage and visual improvement in 51%, 88% and 85% of cases, respectively. Surgery was performed in 29% of cases and all showed tumor remnant and persistent hyperprolactinemia. Women had a lower prolactin level and a smaller tumor diameter at diagnosis but pituitary deficiencies were more frequent and outcome was worse.
CONCLUSION
Giant prolactinomas are rare and have a male predominance. Visual impairment is the most frequent presenting symptom in men and amenorrhea in women. The gender-related difference in tumor size and level of prolactin was confirmed in this analysis where men had a larger diameter and a higher baseline prolactin level. DAs are the treatment of choice, irrespective of tumor size and presence of visual impairment. As only half of the cases achieved normoprolactinemia we do not, in contrast to previous literature, state giant prolactinomas to be exquisitely sensitive to DAs. Patient characteristics associated with persistent hyperprolactinemia after treatment with a DA were female gender, higher baseline prolactin and larger tumor size . This analysis did show TSH- and ACTH-deficiency to be more frequent after surgery which was not seen for LH/FSH deficiency.
Topics: Female; Adult; Male; Humans; Prolactinoma; Pituitary Neoplasms; Hyperprolactinemia; Prolactin; Amenorrhea; Dopamine Agonists; Hypopituitarism; Vision Disorders; Adrenocorticotropic Hormone
PubMed: 37544978
DOI: 10.1007/s11102-023-01337-0 -
Frontiers in Endocrinology 2022Prolactin is a polypeptide hormone that is well known for its role in reproductive physiology. Recent studies highlight its role in neurohormonal appetite regulation and... (Review)
Review
Prolactin is a polypeptide hormone that is well known for its role in reproductive physiology. Recent studies highlight its role in neurohormonal appetite regulation and metabolism. Elevated prolactin levels are widely associated with worsening metabolic disease, but it appears that low prolactin levels could also be metabolically unfavorable. This review discusses the pathophysiology of prolactin related metabolic changes, and the less commonly recognized effects of prolactin on adipose tissue, pancreas, liver, and small bowel. Furthermore, the effect of dopamine agonists on the metabolic profiles of patients with hyperprolactinemia are discussed as well.
Topics: Dopamine Agonists; Humans; Hyperprolactinemia; Pituitary Neoplasms; Prolactin; Prolactinoma
PubMed: 36246929
DOI: 10.3389/fendo.2022.1002320 -
Pituitary Apr 2023Dopamine agonists (DA) are the gold-standard for prolactinoma and hyperprolactinemia treatment. Intolerance to DA leading to drug drop out occurs in 3 to 12% of cases.... (Review)
Review
PURPOSE
Dopamine agonists (DA) are the gold-standard for prolactinoma and hyperprolactinemia treatment. Intolerance to DA leading to drug drop out occurs in 3 to 12% of cases. We provide here a review of published data about DA intolerance and present a case report concerning the use of intravaginal cabergoline.
METHODS
We review the literature on the definition, the pathogenesis, frequency and management of DA intolerance. In addition, the review provides strategies to enhance tolerability and avoid precocious clinical treatment withdrawal.
RESULTS
Cabergoline is often cited as the most tolerable DA and its side effects tend to ameliorate within days to weeks. Restarting the same drug at a lower dose or switching to another DA can be used in cases of intolerance. The vaginal route can be tried specifically if there are gastrointestinal side effects in the oral administration. Symptomatic treatment could be attempted, although mainly based on a strategy used in other diseases.
CONCLUSIONS
Due to limited data, no guidelines have been developed for the management of intolerance in DA treatment. The most frequent management is to perform transsphenoidal surgery. Nevertheless, this manuscript provides data derived from published literature and expert opinion, suggesting new approaches to this clinical issue.
Topics: Female; Humans; Prolactinoma; Dopamine Agonists; Cabergoline; Pituitary Neoplasms; Hyperprolactinemia; Bromocriptine; Ergolines
PubMed: 37027090
DOI: 10.1007/s11102-023-01313-8 -
Biotechnology Journal Jun 2022Electrical stimulation of brain or muscle activities has gained attention for studying the molecular and cellular mechanisms involved in electric-induced responses. We...
Electrical stimulation of brain or muscle activities has gained attention for studying the molecular and cellular mechanisms involved in electric-induced responses. We recently showed zebrafish's response to electricity. Here, we hypothesized that this response is affected by the dopaminergic signaling pathways. The effects of multiple dopamine agonists and antagonists on the electric response of 6 days-postfertilization zebrafish larvae were investigated using a microfluidic device with enhanced control of experimentation and throughput. All dopamine antagonists decreased locomotor activities, while dopamine agonists did not induce similar behaviors. The D2-selective dopamine agonist quinpirole enhanced the movement. Exposure to nonselective and D1-selective dopamine agonists apomorphine and SKF-81297 caused no significant change in the electric response. Exposing larvae that were pretreated with nonselective and D2-selective dopamine antagonists butaclamol and haloperidol to apomorphine and quinpirole, respectively, restored the electric locomotion. These results reveal a correlation between electric response and dopamine signaling pathway. Furthermore, they demonstrate that electric-induced zebrafish larvae locomotion can be conditioned by modulating dopamine receptor functions. Our electrofluidic assay has profound application potential for fundamental electric-induced response research and brain disorder studies especially those related to the dopamine imbalance and as a chemical screening method when investigating biological pathways and behaviors.
Topics: Animals; Apomorphine; Dopamine; Dopamine Agonists; Dopamine Antagonists; Electricity; Larva; Quinpirole; Signal Transduction; Zebrafish
PubMed: 35332995
DOI: 10.1002/biot.202100561 -
Pituitary Jun 2020Hyperprolactinemia is associated with suppression of the hypothalamic- pituitary-gonadal axis and consequent hypogonadism, manifesting loss of libido, infertility and... (Review)
Review
Hyperprolactinemia is associated with suppression of the hypothalamic- pituitary-gonadal axis and consequent hypogonadism, manifesting loss of libido, infertility and osteoporosis long-term in both male and female patients, with associated menstrual irregularities, amenorrhea and galactorrhea in women and erectile dysfunction in men. The primary goals of therapy in patients harboring prolactinoma are control of tumor size and normalization of serum PRL, with restoration of gonadal and sexual function and fertility. Clinical manifestations of hypogonadism have variable consequences depending on the age and sex of the patient and desire for fertility. Careful consideration of clinical consequences of hyperprolactinemia in relation to age and sex should help guide therapeutic decision making. Another important consideration in attaining our treatment goals in patients harboring microprolactinomas, is the observation that greater than 90% of microprolactinomas do not enlarge, when followed for 10 years. Treatment options for the management of microprolactinomas include observation alone, with monitoring of serum prolactin levels every 6-12 months, vs initiation of dopamine agonist therapy vs gonadal steroid hormone replacement (using the oral contraceptive or other combination estrogen and progesterone replacement regimens in females or testosterone replacement therapy in males). In the present review, current data related to clinical consequences of microprolactinomas and treatment outcomes at different stages in the lifespan are reviewed, with a suggested algorithm as to whether to treat or not, and an appropriate therapeutic regimen to institute.
Topics: Dopamine Agonists; Estrogens; Female; Humans; Hypogonadism; Male; Progesterone; Prolactinoma
PubMed: 32274622
DOI: 10.1007/s11102-020-01039-x -
Journal of Neural Transmission (Vienna,... Sep 2022The trajectory of the use of dopamine replacement therapy (DRT) in Parkinson's disease (PD) is variable and doses may need to be increased, but also tapered. The plan... (Review)
Review
The trajectory of the use of dopamine replacement therapy (DRT) in Parkinson's disease (PD) is variable and doses may need to be increased, but also tapered. The plan for dose adjustment is usually done as per drug information recommendations from the licensing bodies, but there are no clear guidelines with regards to the best practice regarding the tapering off schedule given sudden dose reductions of drugs such as dopamine agonists may have serious adverse consequences. A systematic literature search was, therefore, performed to derive recommendations and the data show that there are no controlled studies or evidence-based recommendations how to taper or discontinue PD medication in a systematic manner. Most of the data were available on the dopamine agonist withdrawal syndrome (DAWS) and we found only two instructions on how to reduce pramipexole and rotigotine published by the EMA. We suggest that based on the available data, levodopa, dopamine agonists (DA), and amantadine should not be discontinued abruptly. Abrupt or sudden reduction of DA or amantadine in particular can lead to severe life-threatening withdrawal symptoms. Tapering off levodopa, COMT inhibitors, and MAO-B inhibitors may worsen motor and non-motor symptoms. Based on our clinical experience, we have proposed how to reduce PD medication and this work will form the basis of a future Delphi panel to define the recommendations in a consensus.
Topics: Amantadine; Dopamine; Dopamine Agonists; Humans; Levodopa; Parkinson Disease; Substance Withdrawal Syndrome
PubMed: 34324057
DOI: 10.1007/s00702-021-02389-x