1,405 research outputs found
Metabotropic glutamate receptors and the control of chronic pain
No full textOver the past two decades metabotropic glutamate (mGlu) receptor ligands have been investigated for their potential therapeutic effects in different disorders of the central nervous system (CNS), including anxiety, depression, schizophrenia, and neurodegenerative diseases. In addition, it has been widely demonstrated that mGlu receptors are able to modulate pain transmission both in inflammatory and neuropathic pain models. A large number of preclinical studies combining the use of selective ligands with the knockout strategy have revealed more details about the role of the different mGlu receptor subtypes in the modulation of pain information. This review will address the role of mGlu receptors in pain sensitivity focusing on different strategies to achieve pain control by targeting specific mGlu receptor subtypes. Specifically, pharmacological interventions aimed at inhibiting group I mGlu receptor-mediated signaling and/or potentiating groups II and Ill mGlu receptor signaling together with an epigenetic approach leading to an increased expression of mGlu2 receptors will be discussed
Detection of Inositol Trisphosphate and Other Organic-phosphates By High-performance Liquid-chromatography Using An Enzyme-loaded Postcolumn Reactor
No full text
PERTUSSIS TOXIN INHIBITS SIGNAL TRANSDUCTION AT A SPECIFIC METABOLOTROPIC GLUTAMATE RECEPTOR IN PRIMARY CULTURES OF CEREBELLAR GRANULE CELLS
No full textIn primary cultures of cerebellar granule cells, glutamate receptors have been classified into metabolotropic (G(P1) and G(P2)) and ionotropic (G(C1) and G(C2)). The G(P1) and G(C1) receptors are negatively modulated by magnesium and noncompetitively inhibited by phencyclidine; G(P2) and G(C2) receptors are insensitive to inhibition by magnesium and phencyclidine (Costa, Fadda, Kozikowski, Nicoletti and Wroblewski, 1988). Exposure of cultured cerebellar granule cells to pertussis toxin (PTX, 1 μg/ml for 14-16 hr) reduced the stimulation of the hydrolysis of inositol phospholipids (PI) by the G(P2) receptor agonists, glutamate and quisqualate in the presence of magnesium, but did not inhibit the stimulation of the hydrolysis of PI by G(P1) receptor agonists. The stimulation of the hydrolysis of PI by the muscarinic cholinergic receptor agonist, carbamylcholine, remained unchanged after pretreatment with pertussis toxin. In membranes prepared from cerebellar granule cells in primary culture, the addition of guanosine 5'-0-(3-thiotriphosphate) (GTP-γ-s), a nonhydrolyzable analogue of GTP, enhanced the hydrolysis of PI and reduced the B(max) of quisqualate-displaceable binding of [3H]glutamate. These results indicate that, in primary cultures of cerebellar granule cells, a specific class of metabolotropic glutamate receptors (the G(p2) receptor) is coupled with the hydrolysis of PI through a pertussis toxin-sensitive GTP-binding protein
Effects of repeated administration of estradiol benzoate on tubero-infundibular GABAergic activity in male rats
No full textRepeated (once a day for 8 days) but not single administration of estradiol benzoate (10 μg/kg, s.c.) induced a sevenfold increase in anterior pituitary γ-aminobutyric acid (GABA) concentration in male rats. GABA concentration also increased in the median eminence whereas no changes or decreases were observed in other brain regions including hypothalamic arcuate nucleus, lateral septum, hippocampus, caudate nucleus, and substantia nigra. Eight-day estradiol benzoate injection also enhanced the V(max) of median eminence glutamate decarboxylase activity without affecting the K(m) of the enzyme for glutamic acid. Taken together, these results suggest that repeated administration of estradiol benzoate increases the activity of the tubero-infundibular GABAergic system in male rats
Glycine potentiates the stimulation of inositol phospholipid hydrolysis by excitatory amino acids in primary cultures of cerebellar neurons.
No full textGlycine potentiates stimulation of inositol phospholipid hydrolysis by glutamate and N-methyl-D-aspartate, but not by quisqualate or carbamylcholine, in primary cultures of cerebellar granule cells. This potentiation occurs in the absence of extracellular Mg2+, but is more evident when stimulation of inositol phospholipid hydrolysis by N-methyl-D-aspartate is measured in the presence of 1 mM Mg2+. The action of glycine is not antagonized by strychnine. These results suggest that glycine acts as a positive modulator of signal transduction at a specific class of N-methyl-D-aspartate-sensitive glutamate receptors coupled to inositol phospholipid hydrolysis in cerebellar granule cells
Estradiol benzoate decreases nigral GABAergic activity in male rats.
No full textRepeated doses of estradiol benzoate (10 micrograms/kg, s.c., once a day for 2, 5 or 8 days) to male rats decreased gamma-aminobutyric acid (GABA) content and glutamate decarboxylase (GAD) activity in substantia nigra (SN) but failed to change these parameters in hippocampus, cerebral cortex, cerebellum, lateral septum and olfactory tubercle. In the caudate nucleus, estradiol benzoate decreased GABA concentration but did not modify GAD activity. A decrease in nigral GABA concentration and GAD activity was also observed 24 and 48 but not 3 h after a single injection of estradiol benzoate. These data are consistent with results on GAD activity reported by McGinnis et al. in ovariectomized rats. Kinetic analysis of nigral GAD activity revealed that repeated estradiol benzoate injection reduced the Vmax without affecting the Km of GAD. Estradiol benzoate also reduced the rate of nigral GABA accumulation resulting from local infusion of gabaculine, suggesting that the steroid decreases GABA turnover in male rat SN. Hypophysectomy decreased GABA content and GAD activity in SN and GABA content in striatum. Administration of estradiol benzoate for 8 days to hypophysectomized rats failed to decrease further these parameters. Taken together, these data suggest that estradiol benzoate decreases SN GABAergic activity and that the integrity of the pituitary gland is required for this effect
Depression and Alzheimer's disease: Neurobiological links and common pharmacological targets
No full textDepression is one of the most prevalent and life-threatening forms of mental illnesses, whereas Alzheimer's disease is a neurodegenerative disorder that affects more than 37 million people worldwide. Recent evidence suggests a strong relationship between depression and Alzheimer's disease. A lifetime history of major depression has been considered as a risk factor for later development of Alzheimer's disease. The presence of depressive symptoms can affect the conversion of mild cognitive impairment into Alzheimer's disease. Neuritic plaques and neurofibrillary tangles, the two major hallmarks of Alzheimer's disease brain, are more pronounced in the brains of Alzheimer's disease patients with comorbid depression as compared with Alzheimer's disease patients without depression. On the other hand, neurodegenerative phenomena have been observed in different brain regions of patients with a history of depression. Recent evidence suggests that molecular mechanisms and cascades that underlie the pathogenesis of major depression, such as chronic inflammation and hyperactivation of hypothalamic-pituitary-ad renal (HIPA) axis, are also involved in the pathogenesis of Alzheimer's disease. In particular, a specific impairment in the signaling of some neurotrophins such as transforming-growth-factor beta 1 (TGF-beta 1) and brain-derived neurotrophic factor (BDNF) has been observed both in depression and Alzheimer's disease. In the present review we will examine the evidence on the common molecular pathways between depression and Alzheimer's disease and we will discuss these pathways as new pharmacological targets for the treatment of both major depression and Alzheimer's disease. (C) 2009 Elsevier B.V. All rights reserved
- …
