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Alpha2-delta (alpha2-delta) is a membrane-spanning auxiliary protein subunit of voltage-gated calcium channels found in muscle and brain. Of the four subtypes of alpha2-delta, only alpha2-delta types 1 and 2 (alpha2-delta-1 and alpha2-delta-2) bind the drugs gabapentin (Neurontin) and pregabalin (Lyrica). Although recent findings indicate that drug binding(More)
The modulation of the central cardiovascular effects of alpha2-adrenoceptor activation by oxytocin in the nucleus tractus solitarii has been evaluated by cardiovascular analysis and by quantitative receptor autoradiography. Microinjections in the nucleus tractus solitarii of a threshold dose of oxytocin effectively and significantly counteracted the(More)
The preclinical model of bleomycin-induced lung fibrosis, used to investigate mechanisms related to idiopathic pulmonary fibrosis (IPF), has incorrectly predicted efficacy for several candidate compounds suggesting that it may be of limited value. As an attempt to improve the predictive nature of this model, integrative bioinformatic approaches were used to(More)
Impaired function of the brain vasculature might contribute to the development of HIV-associated dementia. For example, injury or dysfunction of brain microvascular endothelial cells (BMEC) can lead to the breakdown of the blood-brain barrier (BBB) and thus allow accelerated entry of the HIV-1 virus into the CNS. Mechanisms of injury to BMEC during HIV-1(More)
Spinal cord trauma can cause a marked release of free fatty acids, in particular, arachidonic acid (AA), from cell membranes. Free fatty acids, and AA by itself, may lead to secondary damage to spinal cord neurons. To study this hypothesis, cultured spinal cord neurons were exposed to increasing concentrations of AA (0.01-10 microM). AA-induced injury to(More)
Protease-activated receptors (PARs) belong to the family of membrane receptors coupled to G-proteins; their presence is reported in a wide variety of cells. The object of this study was to demonstrate the presence of PAR-1 and PAR-2 in myenteric glia of the guinea pig, and to elucidate the cellular mechanisms that are triggered upon receptor activation.(More)
Hydrolysis of membrane phospholipids of spinal cord neurons is one of the first events initiated in spinal cord trauma. In this process, free fatty acids, and in particular arachidonic acid, are released. Exposure of spinal cord neurons to free arachidonic acid can compromise cell survival and initiate apoptotic cell death. In order to determine potential(More)
Modulation of neurotrophic factor expression may constitute an important part of neuroprotective effects of nicotine. Therefore, the effects of nicotine on expression of nerve growth factor (NGF) and its receptor, tyrosine receptor kinase A (trkA), were studied in cultured spinal cord neurons treated with arachidonic acid. Because injury to spinal cord is(More)
Increased levels of free fatty acids and, in particular, arachidonic acid can lead to induction of apoptosis of spinal cord neurons. Because of the importance of neurotrophic factors in cell survival and death, mRNA and protein levels of brain-derived neurotrophic factor (BDNF) and basic fibroblast growth factor (FGF-2) were studied in cultured spinal cord(More)
Primary spinal cord trauma can trigger a cascade of secondary processes leading to delayed and amplified injury to spinal cord neurons. Release of fatty acids, in particular arachidonic acid, from cell membranes is believed to contribute significantly to these events. Mechanisms of fatty acid-induced injury to spinal cord neurons may include lipid(More)