Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Women undergoing chemotherapy for breast cancer are often administered dopamine antagonist adjuvant medications that may increase levels of prolactin potentially increasing the risk of cancer. Using nationwide computerized registers of death data for the years 1991 through 1996 we examined 12,430,473 deaths of persons over 40 years of age and extracted 144,364 cases with Parkinson's disease (PD), a dopamine deficient population. Patients with PD had lower rates of breast and other types of malignancies, even in the presence of depression and suicide.
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PMID:Are dopamine antagonists a risk factor for breast cancer? An answer from Parkinson's disease. 1465 14

Salsolinol, 1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline, is an endogenous catechol isoquinoline detected in humans by M. Sandler. In human brain, a series of catechol isoquinolines were identified as the condensation products of dopamine or other monoamines with aldehydes or keto-acids. Recently selective occurrence of the (R)enantiomers of salsolinol derivatives was confirmed in human brain, and they are synthesized by enzymes in situ, but not by the non-enzymatic Pictet-Spengler reaction. A (R)salsolinol synthase catalyzes the enantio-specific synthesis of (R)salsolinol from dopamine and acetaldehyde, and (R)salsolinol N-methyltransferase synthesizes N-methyl(R)salsolinol, which is further oxidized into 1,2-dimethyl-6,7-dihydroxyisoquinolinium ion by non-enzymatic and enzymatic oxidation. The step-wise reactions, N-methylation and oxidation, induce the specified distribution of the N-methylated and oxidized derivatives in the human nigro-striatum, suggesting that these derivatives may be involved in the function of dopamine neurons under physiological and pathological conditions. As shown by in vivo and in vitro experiments, salsolinol derivatives affect the levels of monoamine neurotransmitters though the inhibition of enzymes related in the metabolism of catechol- and indoleamines. In addition, the selective neurotoxicity of N-methyl(R)salsolinol to dopamine neurons was confirmed by preparation of an animal model of Parkinson's disease in rats. The involvement of N-methyl(R)salsolinol in the pathogenesis of Parkinson's disease was further indicated by the increase in the N-methyl(R)salsolinol levels in the cerebrospinal fluid and that in the activity of its synthesizing enzyme, a neural (R)salsolinol N-methyltransferase, in the lymphocytes prepared from parkinsonian patients. N-methyl(R)salsolinol induces apoptosis in dopamine neurons, which is mediated by death signal transduction in mitochondria. In addition, salsolinol was found to function as a signal transmitter for the prolactin release in the neuro-intermediate lobe of the brain. These results are discussed in relation to role of dopamine-derived endogenous salsolinol derivatives as the regulators of neurotransmission, dopaminergic neurotoxins and neuro-hormonal transmitters in the human brain.
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PMID:Dopamine-derived salsolinol derivatives as endogenous monoamine oxidase inhibitors: occurrence, metabolism and function in human brains. 1469 94

The endogenous cannabinoid system is a new signaling system composed by the central (CB1) and the peripheral (CB2) receptors, and several lipid transmitters including anandamide and 2-arachidonylglycerol. This system is the target of natural cannabinoids, the psychoactive constituents of Cannabis sativa preparations (marijuana, hashish). Acute and chronic cannabis exposure has been associated with subjective feelings of pleasure and relaxation, but also to the onset of psychiatric syndromes, a decrease of the efficacy of neuroleptics and alterations in the extrapyramidal system regulation of motor activity. These actions point to a tight association of the cannabinoid system with the brain dopaminergic circuits involved in addiction, the clinical manifestation of positive symptoms of schizophrenia and Parkinson's disease. The present work discusses anatomical, biochemical and pharmacological evidences supporting a role for the endogenous cannabinoid system in the modulation of dopaminergic transmission. Cannabinoid CB1 receptors are present in dopamine projecting brain areas. In primates and certain rat strains it is also located in dopamine cells of the A8, A9 and A10 mesencephalic cell groups, as well as in hypothalamic dopaminergic neurons controlling prolactin secretion. CB1 receptors co-localize with dopamine D1/D2 receptors in dopamine projecting fields. Manipulation of dopaminergic transmission is able to alter the synthesis and release of anandamide as well as the expression of CB1 receptors. Additionally, CB1 receptors can switch its transduction mechanism to oppose to the ongoing dopamine signaling. Acute blockade of CB1 receptor potentiates the facilitatory role of dopamine D2 receptor agonists on movement. CB1 stimulation results in sensitization to the motor effects of indirect dopaminergic agonists. The dynamics of these changes indicate that the cannabinoid system is an activity-dependent modulator of dopaminergic transmission, an hypothesis relevant for the design of new therapeutic strategies for dopamine-related diseases such as the psychosis and Parkinson's disease.
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PMID:Role of the endogenous cannabinoid system as a modulator of dopamine transmission: implications for Parkinson's disease and schizophrenia. 1511 Dec 59

Age-related depletion of testosterone may increase the brain's vulnerability to parkinsonian- or Alzheimer's-like neurodegenerative disorders. In rats, rotenone, a mitochondrial complex I inhibitor, causes specific nigral dopaminergic neurodegeneration producing parkinsonian symptoms. In this study, rotenone was administered on a daily basis (2 mg/kg i.p.) to two groups of rats, over a period of 30 and 60 days, respectively. In order to contribute towards the validation of the rotenone rat model, the changing level of the peripheral sex steroid hormone, testosterone, which would also mimic those found in Parkinson's disease (PD) patients, was evaluated. Parallel to this, prolactin, luteinizing hormone (LH), the nonsexual steroid thyroid-stimulating hormone, and the corticosterone hormone levels in the peripheral blood plasma were measured to show whether other hormones have also been affected by complex I inhibition. The rotenone treatment caused a decrease of testosterone level in the peripheral blood plasma. There were no differences in the thyroid hormone and prolactin but increases in leutinizing hormone and corticosterone were observed. Data from this study indicate that rotenone depleted the sex steroid hormone which is preferentially produced in the periphery, e.g., adrenal gland and testis. In conclusion, because a decrease in testosterone levels is also one of the comorbidities which are found in male PD patients, our results indicate that the rotenone model mimics PD symptoms not only on a neuronal and behavioral level, but also on the testosterone levels.
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PMID:Mitochondrial complex I inhibition depletes plasma testosterone in the rotenone model of Parkinson's disease. 1558 61

The purpose of this study is to demonstrate that sumanirole is a novel dopamine receptor agonist with high in vitro and in vivo selectivity for the D(2) receptor subtype. Sumanirole, (R)-5,6-dihydro-5-(methylamino)-4H-imidazo[4,5,1-ij]quinolin-2(1H)-one (Z)-2-butenedioate (1:1), is unique; it has greater than 200-fold selectivity for the D(2) receptor subtype versus the other dopamine receptor subtypes in radioligand binding assays. In cell-based assays, sumanirole is a fully efficacious agonist, with EC(50) values between 17 and 75 nM. In animals, sumanirole elicits many physiological responses attributed to D(2)-like receptor function. In rats, sumanirole is a full agonist for elevation of striatal acetylcholine levels (ED(50) = 12.1 micromol/kg i.p.). Sumanirole s.c. dose dependently decreased plasma prolactin levels and depressed dopamine neuron firing rates in the substantia nigra pars compacta with an ED(50) of 2.3 micromol/kg i.v. This high selectivity for D(2) receptors translates into excellent locomotor stimulant activity in animal models of Parkinson's disease. In reserpinized, alpha-methyl-para-tyrosine-treated rats, sumanirole caused a significant and sustained increase in horizontal activity at doses > or =12.5 micromol/kg s.c. In unilateral 6-hydroxydopamine-lesioned rats, sumanirole caused profound, sustained rotational behavior and was substantially more efficacious than any other agonist tested. Sumanirole-stimulated rotational behavior was blocked by the dopamine receptor antagonist haloperidol. Sumanirole dose dependently improved disability scores and locomotor activities of two of three 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned monkeys. In summary, sumanirole is the first published selective D(2) receptor agonist. The compound has activity in animal models of dopamine hypofunction and has a high level of efficacy in animal models of Parkinson's disease.
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PMID:Sumanirole, a highly dopamine D2-selective receptor agonist: in vitro and in vivo pharmacological characterization and efficacy in animal models of Parkinson's disease. 1598 60

Catecholamine (dopamine, norepinephrine and epinephrine) synthesizing neurons are widely distributed in the brain, sympathetic ganglia and throughout peripheral organs. Results of several recent experiments clearly suggest that many of these neurons can also contain 1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (salsolinol), a derivate of dopamine. However, direct proof of salsolinol synthesis in those neurons is still missing. The data obtained with administration of exogenous salsolinol strongly indicate that it may play an important role in catecholaminergic regulatory processes, such as the regulation of prolactin release and/or neuronal transmission in sympathetic ganglia. Several recent data have also indicated a relationship between salsolinol or its metabolites and the etiology of Parkinson's disease or neuropathology of chronic alcoholism. These seemingly different roles of salsolinol will be discussed separately, but some common features will also be highlighted. Based on all of the discussed data the existence of a "salsolinolergic" system using salsolinol as a neuromodulator, which may be present in catecholamine synthesizing neurons, is postulated.
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PMID:Salsolinol, a derivate of dopamine, is a possible modulator of catecholaminergic transmission: a review of recent developments. 1623 67

Sperm protein 22 (SP22) was recently identified in the anterior pituitary gland (AP) of male Golden Syrian hamsters using ion trap mass spectrometry. SP22 has been implicated in apoptosis, androgen receptor function, fertility, and ontogeny of early-onset Parkinson's disease. However, the role of SP22 in the pituitary has not been investigated. We cloned the cDNA for full-length SP22 from AP and posterior lobe (posterior pituitary and intermediate lobe) of the pituitary gland in adult male rats and Golden Syrian hamsters, confirming the presence of SP22 mRNA in the AP and posterior lobe. Because gonadal steroids are important regulators of AP function, and SP22 is associated with androgen receptor function, we used Western blots to compare SP22 in the AP of intact and orchidectomized male rats given placebo or a low or high dose of testosterone. SP22 did not differ with treatment, indicating that AP SP22 concentration was not regulated by testosterone. To localize SP22 to specific cells of the AP, mirror-image paraffin sections were labeled against SP22 and either luteinizing hormone (LH)beta, thyroid-stimulating hormone (TSH)beta, prolactin, adrenocorticotropic hormone (ACTH), or growth hormone (GH) using peroxidase-conjugated secondary antibody. Additional sections were colabeled with SP22 and one of the AP hormones using fluorescent secondary antibodies. SP22 colocalized in somatotropes and thyrotropes in rat and hamster. We identified SP22 in a small percentage of corticotropes, gonadotropes, and lactotropes. This is the first report that SP22 mRNA is present specifically in the AP, and SP22 is localized primarily in somatotropes and thyrotropes. SP22 may help regulate AP function and be particularly important for the control of GH and TSH secretion.
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PMID:Localization of fertility factor SP22 to specific cell types within the anterior pituitary gland. 1624 99

Delirium, depression and other psychiatric difficulties are commonly encountered by posttransplantation patients, and antipsychotic medicines are frequently used to treat these difficulties. This article reviews previous research data concerning the immunological effects of these medicines, with particular focus on the consequences of prolactin elevation. Unproven but of concern is that these effects may influence graft fate. Older antipsychotic medicines such as haloperidol and chlorpromazine have a high likelihood of elevating prolactin. Prolactin is an immunologically active molecule generally promoting bone marrow function. This may be of benefit post-stem-cell transplant, helping engraftment, but could further rejection of solid-organ transplants. Elevated prolactin is implicated in the facilitation of graft-versus-host disease. Aripiprazole is the antipsychotic medicine least likely to increase prolactin (and may actually decrease prolactin); risperidone, the most likely to increase prolactin. Olanzapine, quetiapine and ziprazadone are antipsychotic medicines with a lower likelihood of elevating prolactin. Older ("neuroleptic") antipsychotics, such as chlorpromazine, droperidol and haloperidol, perphenazine and many others, are likely to elevate serum prolactin. Among antidepressants, most serotonin reuptake inhibitors, with the exception of sertraline, can slightly elevate prolactin. The atypical (i.e., alone in their class) antidepressants bupropion and mirtazapine are prolactin neutral. The immunological consequences of psychiatric medicines should be considered when treating transplant patients for delirium, depression and thought disorders; in addition, if elevation of prolactin is thought to be of immunological importance during psychiatric treatment, then it should be monitored and treated. The dopamine agonists used to treat Parkinson's disease--bromocriptine, pergolide, pramipexole, ropinerole--usually reverse antipsychotic-induced prolactin increases without compromising psychiatric effectiveness.
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PMID:Review of evidence that posttransplantation psychiatric treatment commonly affects prolactin levels and thereby influences graft fate. 1667 66

Weight gain is a common adverse effect associated with the use of most typical and atypical antipsychotic. Aim of this study was to investigate serum prolactin, leptin, cholesterol, triglyceride, lipoproteins, such high density lipoprotein (HDL), and low density lipoprotein (LDL) levels in patients with Parkinson's disease (PD)-related psychosis during long-term medication with atypical antipsychotic. The study population comprised 40 patients, who were divided into 4 groups: olanzapine (n=10), risperidone (n=10), seroquel (n=10) monotherapy, a group of 10 patients receiving only antiparkinson drugs and a control group of 8 healthy persons. The patients were evaluated at baseline and at the sixth and twelfth week according to the Positive and Negative Syndrome Scale (PANSS), body mass index (BMI), and fasting serum prolactin, leptin, lipids and lipoproteins levels. Treatment of patients with olanzapine caused marked increase of serum LDL, cholesterol, triglyceride, and leptin levels (p<0,02). No changes in HDL concentrations. There was positive relationship between serum leptin, lipid levels and BMI. However, treatment of patients with seroquel did not cause changes in serum prolactin, leptin, lipids, and lipoproteins levels. Our results suggest that treatment of patients with PD-related psychosis with seroquel appears to have minimal influence on serum leptin, prolactin, lipids, lipoproteins and BMI compared with olanzapine and risperidone.
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PMID:Serum prolactin, leptin, lipids and lipoproteins levels during antipsychotics treatment in Parkinson's disease and related psychosis. 1676 9

Levodopa, when combined with a decarboxylase inhibitor, essentially delivers dopamine directly to the brain, with no net effect on brain blood vessels. For future neuroimaging studies of Parkinson disease and Tourette syndrome, we sought to rapidly produce a biologically relevant levodopa concentration in plasma and then maintain that concentration long enough to assess motor, cognitive, emotional, and neuroimaging responses, while minimizing side effects in levodopa-naive individuals. Based on available pharmacokinetic data and a two-compartment model, we designed a decreasing-exponential-rate infusion to meet these goals. This report gives results of double-blind levodopa and placebo infusions in six healthy subjects. Mean plasma levodopa concentrations were within 3% of their 1200 ng/mL target at 20 and 40 min into the infusion, and within 20% between approximately 12 and 90 min. Levodopa significantly reduced serum prolactin and raised serum growth hormone concentrations. Volunteers had no significant side effects.
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PMID:Intravenous levodopa administration in humans based on a two-compartment kinetic model. 1693 32


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