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

In order to test possible changes in the stimulating effect of intravenously-infused substance P (SP) on ACTH/cortisol and GH secretion in Parkinson's disease, 10 male parkinsonian patients and 10 age-matched normal controls were infused intravenously for 60 min with SP (1.0 or 1.5 pmol/kg-1/min-1 SP) or normal saline. The circulating levels of ACTH, cortisol and GH were measured during and for 20 min after SP or saline infusion. No untoward side effects or changes in blood pressure were observed during SP infusion in any subjects. In basal conditions and during saline infusion, plasma ACTH and cortisol levels were similar in normal and parkinsonian patients. During SP infusions, ACTH/cortisol concentrations in normal controls rose significantly vs baseline and saline test in a dose-dependent fashion. In contrast, at both SP infused amounts, parkinsonian patients showed ACTH/cortisol levels similar to those observed in the saline test. All subjects showed similar basal concentrations of GH. GH levels rose significantly in the normal controls when the higher dose of SP was infused, but they were not modified by the infusion of the lower dose of SP or saline. At both tested amounts of SP and during saline infusion, GH levels remained unchanged in the parkinsonian subjects. In agreement with previous observations in the literature showing SP abnormalities in the parkinsonian brain, these data fail to show significant effects of plasma SP on the ACTH/cortisol and GH secretory systems in Parkinson's disease.
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PMID:Lack of ACTH/cortisol and GH responses to intravenously-infused substance P in Parkinson's disease. 750 7

We used the PCR amplification technique in an attempt to characterize further the dopamine D2L receptor expressed in the prolactin-secreting pituitary MMQ cell clone, derived from the prolactin- and ACTH-secreting Buffalo rat 7315 alpha pituitary tumour. By semiquantitative PCR amplification we were unable to detect the mRNA encoding the D2S receptor isoform, which derives from the well-known process of alternative splicing, producing two D2 receptor subtypes (D2L and D2S) in such tissues as the anterior pituitary and the corpus striatum. Although the pharmacology of the D2 receptor has been established in many studies on both native receptors and transfected receptor isoforms, because of the lack of tissues naturally expressing only one receptor isoform, MMQ cells represent the first example of cells uniquely or prevalently expressing only the D2L receptor, conceivably coupled to its native transduction mechanisms. These considerations prompted us to evaluate the pharmacology and the second messenger systems known to be modulated by dopamine. Scatchard analysis of [3H]spiperone binding resulted in a linear plot, consistent with the existence of a single class of binding sites, with a Kd of 0.055 +/- 0.002 nM and a Bmax of 27 +/- 3.5 fmol/mg protein. Competition experiments confirmed the GTP-dependence and the order of potency for agonist and antagonist ligands consistent with binding to a D2 receptor. The inhibitory effects of dopamine on adenylyl cyclase activity, inositol phosphate production and intracellular free calcium concentrations, the latter presumably via the opening of K+ channels, and prolactin secretion, as well as the reversal of the effect by the D2-selective antagonist (-)sulpiride and pretreatment with pertussis toxin, are consistent with the known biological actions of dopamine at D2 receptors. Based on our observations, the MMQ cell line can be considered a useful tool for investigating ligand-receptor interactions to develop new selective dopaminergic D2L ligands for the therapy of dopamine-related disorders such as schizophrenia, depression, Parkinson's disease and drug addiction.
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PMID:Absence of D2S dopamine receptor in the prolactin-secreting MMQ pituitary clone: characterization of a wild D2L receptor coupled to native transduction mechanisms. 766 27

Naloxone is unable to stimulate ACTH/cortisol secretion in patients with de novo Parkinson's disease, suggesting a reduced endogenous opioid control of the hypothalamic-pituitary-adrenal axis in parkinsonian patients. In the present study we examined whether Parkinson's disease also impairs the secretion of LH, which is under the inhibitory control of different opioid peptides than ACTH/cortisol. In addition, we examined whether a chronic dopaminergic therapy for at least one year with levodopa (450 mg/day) plus benserazide (112.5 mg/day) in 3 divided oral doses/day of Madopar modifies the ACTH/cortisol and/or the LH response to naloxone (4 mg as an i.v. bolus plus 10 mg infused in 2 hours). Ten parkinsonian patients (aged 52-62 years) and 8 normal controls (50-60 years) were tested with naloxone and in a different occasion with normal saline. The parkinsonian patients were tested both before and after dopaminergic treatment. Tests started at 09.00 h and lasted 2.5 hours. Basal ACTH/cortisol and LH levels were similar in all groups. During saline tests, ACTH/cortisol levels showed a slight physiological decline in all groups, whereas LH levels remained constant. Naloxone administration significantly increased the plasma levels of ACTH/cortisol and LH in the normal controls, but not in the parkinsonian patients before the dopaminergic treatment. In contrast, dopaminergic therapy restored significant ACTH/cortisol and LH responses to naloxone in parkinsonian patients. In fact, after levodopa plus benserazide, naloxone-induced ACTH, cortisol and LH increments in parkinsonian patients were significantly higher than before therapy and were indistinguishable from those observed in the normal controls. These data suggest that in men Parkinson's-related dopaminergic alterations may underlie the defective endogenous opioid control of ACTH/cortisol and LH secretion.
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PMID:Restoration of ACTH/cortisol and LH responses to naloxone by chronic dopaminergic treatment in Parkinson's disease. 857 65

Parkinson's disease (PD) is characterized by a markedly decreased number of nigrostriatal dopaminergic neurons. The pathogenesis of PD is still unknown; among other etiological factors, immunological abnormalities have been suggested. Recently, interleukin-2 (IL-2) has been hypothesized to be an endogenous cytokine that regulates striatal dopaminergic function. We examined the plasma concentrations of IL-1, IL-2, IL-6 and blood levels of ACTH, cortisol and prolactin of 21 patients with PD without any previous treatment. Age- and sex-matched subjects without any neurological or immune disorders were used as controls. Significantly higher serum concentrations of IL-2 in patients with PD were found. Treatment with antiparkinsonian drugs reduced IL-2 levels in these patients. Our results suggested a functional relationship between central dopaminergic and immune systems and a possible involvement of the latter in the pathogenesis of PD.
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PMID:Evaluation of interleukins, ACTH, cortisol and prolactin concentrations in the blood of patients with parkinson's disease. 894 28

In order to establish whether the serotonergic disorder affecting the parkinsonian brain also modifies hypothalamic-pituitary function in Parkinson's disease, 10 patients (aged 57-66 years) and 10 normal controls (aged 55-69 years) were tested with the serotonergic agonist d,l-fenfluramine (60 mg p.o.), with CRH (100 micrograms i.v.) and with placebos. Plasma ACTH/cortisol levels during tests were evaluated and compared. Both groups showed similar levels of ACTH and cortisol in basal conditions and after placebo administration. A slight physiological decline in both ACTH and cortisol levels during the placebo test was observed in normal controls and parkinsonian patients. CRH induced similar ACTH/cortisol increments in all subjects. In contrast, d,l-fenfluramine significantly increased plasma ACTH/cortisol concentrations in the normal controls, but not in the parkinsonian patients. These data show a defective serotonergic control of the pituitary-adrenal axis in Parkinson's disease.
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PMID:ACTH/cortisol involvement in the serotonergic disorder affecting the parkinsonian brain. 909 97

Yawning is considered a brainstem regulated behavior which is associated with changes in arousal and activity levels. Yawning and stretching are dopamine (DA) mediated behaviors and pharmacological studies indicate that these behaviors are associated with increased DA release coupled with stimulation of postsynaptic DA-D2 receptors. Despite their relation to the dopaminergic system, yawning and stretching are poorly documented in untreated or treated patients with Parkinson's disease (PD). A 49 year old fully medicated female patient with juvenile onset PD is presented in whom recurrent episodes of yawning and stretching developed during transcranial administration of AC pulsed electromagnetic fields (EM Fs) of picotesla flux density. These episodes have not been observed previously in this or other patients during treatment with levodopa or DA receptor agonists or in unmedicated PD patients during treatment with AC pulsed EMFs. It is suggested that yawning and stretching behavior resulted in this patient from a synergistic interaction between EMFs and DA derived from levodopa supplementation with EMFs possibly facilitating the release of DA and simultaneously activating postsynaptic DA-D2 receptors in the nigrostriatal dopaminergic pathways. In addition, it is postulated that the release of ACTH/MSH peptides from peptidergic neurons in the brain upon stimulation of the DA-D2 receptors reinforced the yawning and stretching behavior.
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PMID:Yawning and stretching induced by transcranial application of AC pulsed electromagnetic fields in Parkinson's disease. 1068 Nov 23

YAWNING IS A COMMON PHYSIOLOGICAL EVENT THAT CAN BE DIVIDED INTO THREE DISTINCT PHASES: a long inspiratory phase, a brief acme and a rapid expiration. The aim of yawning is not yet well defined. However this semi-voluntary event increases vigilance and aims to alert when drowsiness occurs. Yawning probably has an important role for social communication as well. Yawning can be responsible for pain, luxation or even transient ischaemic attack. Abnormal yawning is present in various pathologies: migraine, Parkinson's disease, tumours, psychiatric diseases, infections or iatrogenic pathologies. The neuro-pharmacology of yawning is complex and knowledge of its mechanisms is incomplete. While under the control of several neurotransmitters, yawning is largely affected by dopamine. Dopamine may activate oxytocin production in the paraventricular nucleus of the hypothalamus. Oxytocin may then activate cholinergic transmission in the hippocampus and, finally, acetylcholine might induce yawning via the muscarinic receptors of the effectors. This is an over-simplification; many other molecules can modulate yawning, such as nitric oxide, glutamate, GABA, serotonin, ACTH, MSH, sexual hormones and opium derivate peptides. Dopamine involvement in yawning could have practical applications in the study of new drugs or the exploration of neurological diseases such as migraine or psychosis. 2001 Harcourt Publishers Ltd
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PMID:Yawning. 1253 Sep 94

Elevated levels of oxidative stress and neuronal inflammation in the hypothalamus or ventral midbrain, respectively, represent common denominators for obesity and Parkinson's Disease (PD). However, little is known about defense mechanisms that protect neurons in these regions from oxidative damage. Here, we aimed to assess whether murine Gpx4, a crucial antioxidant enzyme that protects neurons from membrane damage and ferroptosis, is critical for the protection from neuronal inflammation in two distinct pathophysiologic diseases, namely metabolic dysfunction in diet-induced obesity or PD. Gpx4 was deleted from either AgRP or POMC neurons in the hypothalamus, essential for metabolic homeostasis, or from dopaminergic neurons in the ventral midbrain, governing behaviors such as anxiety or voluntary movement. To induce a pro-inflammatory environment, AgRP and POMC neuron-specific Gpx4 knockout mice were subjected to high-fat high-sucrose (HFHS) diet. To exacerbate oxidative stress in dopaminergic neurons of the ventral midbrain, we systemically co-deleted the PD-related gene DJ-1. Gpx4 was dispensable for the maintenance of cellular health and function of POMC neurons, even in mice exposed to obesogenic conditions. In contrast, HFHS-fed mice with Gpx4 deletion from AgRP neurons displayed increased body adiposity. Gpx4 expression and activity were diminished in the hypothalamus of HFHS-fed mice compared to standard diet-fed controls. Gpx4 deletion from dopaminergic neurons induced anxiety behavior, and diminished spontaneous locomotor activity when DJ-1 was co-deleted. Overall, these data suggest a physiological role for Gpx4 in balancing metabolic control signals and inflammation in AgRP but not POMC neurons. Moreover, Gpx4 appears to constitute an important rheostat against neuronal dysfunction and PD-like symptoms in dopaminergic circuitry within the ventral midbrain.
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PMID:Alterations in neuronal control of body weight and anxiety behavior by glutathione peroxidase 4 deficiency. 2862 18

Parkinson's disease (PD) is the second most common severe neurodegenerative disorder that is characterized by progressive degeneration of dopaminergic neurons (DA neurons) in the substantia nigra pars compacta (SNpc) region of the brain. In the present study, we investigated the effects of the synthetic regulatory peptides Semax (analog of an ACTH 4-10 fragment (ACTH4-10)) and Selank (analog of immunomodulatory taftsin) on behavior of rats with 6-hydroxidopamine (6-OHDA) induced PD-like parkinsonism. It was showed that both peptides did not affect motor activity of rats in elevated cross shaped maze and passive defensive behavior of the animals. At the same time, Selank decreased level of anxiety of rats with toxic damage of DA neurons in elevated cross shaped maze. Previously such effects of Selank were revealed in healthy rodents (rats and mice) with different models of psycho-emotional stress. Therefore, toxic damage of substantia nigra does not affect the response of the rat organism on this peptide.
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PMID:Peptides semax and selank affect the behavior of rats with 6-OHDA induced PD-like parkinsonism. 2870 21


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