RESUMO
The Cl- secretory pathway that is defective in cystic fibrosis (CF) can be bypassed by an alternative pathway for Cl- transport that is activated by extracellular nucleotides. Accordingly, the P2 receptor that mediates this effect is a therapeutic target for improving Cl- secretion in CF patients. In this paper, we report the sequence and functional expression of a cDNA cloned from human airway epithelial (CF/T43) cells that encodes a protein with properties of a P2U nucleotide receptor. With a retrovirus system, the human airway clone was stably expressed in 1321N1 astrocytoma cells, a human cell line unresponsive to extracellular nucleotides. Studies of inositol phosphate accumulation and intracellular Ca2+ mobilization induced by extracellular nucleotides in 1321N1 cells expressing the receptor identified this clone as the target receptor in human airway epithelia. In addition, we independently isolated an identical cDNA from human colonic epithelial (HT-29) cells, indicating that this is the same P2U receptor that has been functionally identified in other human tissues. Expression of the human P2U receptor (HP2U) in 1321N1 cells revealed evidence for autocrine ATP release and stimulation of transduced receptors. Thus, HP2U expression in the 1321N1 cell line will be useful for studying autocrine regulatory mechanisms and in screening of potential therapeutic drugs.
Assuntos
Canais de Cloreto/genética , Receptores de Superfície Celular/genética , Receptores Purinérgicos P2/genética , Trifosfato de Adenosina/farmacologia , Sequência de Aminoácidos , Sequência de Bases , Cálcio/metabolismo , Carbacol/farmacologia , Clonagem Molecular , Primers do DNA/química , DNA Complementar/genética , Expressão Gênica , Genes , Humanos , Fosfatos de Inositol/metabolismo , Dados de Sequência Molecular , RNA Mensageiro/genética , Receptores Purinérgicos P2/metabolismo , Receptores Purinérgicos P2Y2 , Transdução de Sinais , Distribuição Tecidual , Uridina Trifosfato/farmacologiaRESUMO
Migraine occurring at menstruation is frequently difficult to treat. A 38-year-old woman with exceptionally severe menstrual migraine was treated by temporary ovarian suppression using Zoladex, a long acting luteinizing hormone-releasing hormone agonist. There was prompt relief of headache, and after several months of treatment the patient elected to undergo surgical oophorectomy with subsequent resolution of her migraine. A trial of reversible hypogonadism using an LHRH agonist may thus be helpful in predicting the result of surgical castration in this situation.
Assuntos
Busserrelina/análogos & derivados , Menstruação , Transtornos de Enxaqueca/tratamento farmacológico , Adulto , Busserrelina/administração & dosagem , Busserrelina/farmacologia , Busserrelina/uso terapêutico , Estradiol/sangue , Feminino , Hormônio Foliculoestimulante/sangue , Gosserrelina , Humanos , Injeções Subcutâneas , Hormônio Luteinizante/sangue , Transtornos de Enxaqueca/sangue , Transtornos de Enxaqueca/etiologiaRESUMO
Methemoglobin levels have been found to vary with altitude and to shift the hemoglobin-oxygen dissociation curve. In this study, hematocrits and methemoglobin levels were monitored in rats exposed to hypoxia (420 torr absolute) for various intervals. Hematocrits gradually increased throughout the period of hypoxia, while methemoglobin levels rose by 12 h, peaked at 24 h and returned to control level by day 6. These data, in the context of other work, suggest that increased methemoglobin is important in acclimation to hypoxia.
