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ATP-gated P2X4 receptors (P2X4R) are abundantly expressed in the CNS. However, little is known about the molecular targets for ethanol action in P2X4Rs. The current investigation tested the hypothesis that the ectodomain-transmembrane (TM) interface contains residues that are important for the action of ethanol in P2X4Rs. Wild type (WT) and mutant P2X4R were expressed in Xenopus oocytes. ATP concentration–response curves and ethanol (10–200 mM)-induced changes in ATP EC10-gated currents were determined using two-electrode voltage clamp (−70 mV). Alanine substitution at the ectodomain-TM1 interface (positions 50–61) resulted in minimal changes in ethanol response. On the other hand, alanine substitution at the ectodomain-TM2 interface (positions 321–337) identified two key residues (D331 and M336) that significantly reduced ethanol inhibition of ATP-gated currents without causing marked changes in ATP I max, EC50, or Hill's slope. Other amino acid substitutions at positions 331 and 336 significantly altered or eliminated the modulatory effects of ethanol. Linear regression analyses revealed a significant relationship between hydropathy and polarity, but not molecular volume/molecular weight of the residues at these two positions. The results support the proposed hypothesis and represent an important step toward developing ethanol-insensitive receptors for investigating the role of P2X4Rs in mediating behavioral effects of ethanol.  相似文献   
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Bronchopulmonary dysplasia (BPD) is a chronic lung disease affecting premature infants with long term effect on lung function into adulthood. Multiple factors are involved in the development of BPD. This review will summarize the different mechanisms leading to this disease and highlight recent bench and clinical research targeted at understanding the role of the mesenchyme (both its cellular and extracellular components) in the pathogenesis of BPD.  相似文献   
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Activity of propriospinal neurons in segments C3 and C4 was recorded in immobilized decerebrate cats, whose spinal cord was divided at the lower thoracic level, during locomotor activity of neuronal mechanisms controlling the forelimbs (fictitious locomotion of the forelimbs). Neurons were identified according to antidromic responses to stimulation of the lateral column of the spinal cord at level C6. Antidromic responses also appeared in 70% of these neurons to stimulation of the medullary lateral reticular nucleus. During fictitious locomotion, i.e., in the absence of afferent signals from the limb receptors, rhythmic modulation of the discharge of most neurons was observed, correlating with activity of motoneurons. If the rostral region of the cervical enlargement of the spinal cord was cooled, causing generation of the locomotor rhythm to cease, rhythmic activity of propriospinal neurons in segments C3 and C4 also ceased. The main source of modulation of activity of propriospinal neurons in segments C3 and C4 is thus the central spinal mechanisms controlling activity of the forelimbs.Institute for Problems in Information Transmission, Academy of Sciences of the USSR, Moscow. M. V. Lomonosov Moscow University. Translated from Neirofiziologiya, Vol. 17, No. 3, pp. 320–326, May–June, 1985.  相似文献   
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Dynamics of the expression of MHC class I, immune proteasomes and proteasome regulators 19S, PA28, total proteasome pool and proteasome chymotrypsin-like activity in Walker 256 tumor after implantation into Brattleboro rats with the hereditary defect of arginine-vasopressin synthesis was studied. The tumor growth and regression in Brattleboro rats were accompanied by changes in the proteasome subunit level unlike the tumor growth in WAG rats with normal expression of arginine-vasopressin gene. In the tumor implanted into Brattleboro rats the immune proteasome level was maximal between days 14 and 17, when the tumor underwent regression. Conversely, the expression of proteasome regulators tended to decrease during this period. Immune proteasomes are known to produce antigen epitopes for MHC class I to be presented to CD8+ T lymphocytes. Enhanced expression of immune proteasomes coincided with the recovery of MHC class I expression, suggesting the efficient presentation of tumor antigens in Brattleboro rats.  相似文献   
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