ISSN:1062-4821    

出版商:OVID    

年代:1993

数据来源: OVID

ISSN:1062-4821    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

The movement of water across cell membranes has been an active area of research for more than 100 years and is of fundamental importance in the normal water metabolism of all terrestrial animals. The objective of this review is to integrate recent data obtained from the isolation and molecular cloning of water channel proteins, with functional information provided by biophysical measurements of membrane water transport. Whereas the water permeability of most cell membranes can be accounted for by the diffusion of water across the lipid bilayer, other cells, including the erythrocyte as well as certain cells in renal epithelia, possess specialized water channels. Water channels are composed of specialized proteins that create highly selective aqueous pores across cell membranes. Data concerning the distribution, permeability, and function of these various water channels will greatly enhance our knowledge of how water is transported across cell membranes.

ISSN:1062-4821    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

The Na+/H+exchangers are vital transmembrane transporters that participate in the regulation of intracellular pH and volume as well as transepithelial ion transport. Several isoforms of these antiporters belonging to the same gene family have been cloned, and they display tissue-specific expression. All these transporters are highly regulated via various stimuli, which can modulate their activity and expression level. Impairments in regulation of the antiporters may contribute to certain pathologic situations. Biochemical techniques and the tools of molecular genetics now provide the means to analyze the different aspects of these transporters at a molecular level.

ISSN:1062-4821    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Two proton-transporting ATPases participate in active proton transport in the nephron: the electrogenic vacuolar H+-ATPase and the electroneutral H+-K+-ATPase. The vacuolar H+-ATPase participates in proximal and distal hydrogen ion secretion related to acid-base homeostasis. The H+-K+-ATPase is located exclusively in the distal nephron, and its primary role may be in active potassium reabsorption. The properties, distribution, and regulation of these two enzymes are discussed.

ISSN:1062-4821    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

The sodium pump Na, K-ATPase, a heterodimer of an a catalytic subunit and a β glycoprotein subunit, is regulated by a wide array of hormonal, autocrine, and paracrine factors. Both short-term acute adjustments of activity and long-term adjustments of sodium pump pool size are important determinants of cellular Na, K-ATPase activity. Phosphorylation and dephosphorylation are implicated in the acute regulation of activity. Although there is not yet any direct demonstration of phosphorylationin vivo, in vitrostudies on purified enzyme directly demonstrate that phosphorylation decreases Na, K-ATPase activity. In addition, it is likely that phosphorylation of other proteins regulates sodium pump activity and cellular distribution. In regard to long-term regulation, recent demonstration of differential translatability of α and β mRNAs and differential stability of newly synthesized α and β subunits suggests that β subunit is synthesized in excess over α subunit and that the excess is rapidly degraded. The isoform composition of α β heterodimers has been shown to affect enzymatic properties, and tissue-specific heterodimer patterns are emerging from regulation studies. In regard to Na, K-ATPase and hypertension, there is continued interest in the significance of the uncoupling of dopamine inhibition of proximal tubule Na, K-ATPase activity in hypertensive rat strains. The uncoupling has been shown to be specific to the proximal tubule, which has been shown to express DA1 dopamine receptors, and both receptor and postreceptor defects are implicated. Questions remaining include how activation of dopamine receptors is coupled to decreased sodium transporter expression in the proximal tubule (short- and long-term regulation) in normotensive rats, the precise nature of the defect in hypertension, and whether a similar defect is observed in human hypertensive patients.

ISSN:1062-4821    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

The emergence of multidrug resistance in tumor cells is caused by the expression of P-glycoprotein. P-glycoprotein has a unique structure formed by two homologous halves, each encoding six putative transmembrane segments and one nucleotide binding fold. This structural arrangement has been conserved in a large number of eukaryotic and prokaryotic membrane transport systems, which together form the ATP binding cassette superfamily. These membrane transporters act on different groups of substrates in different cell types and organisms. The combined molecular analysis of these proteins has shed light on the mechanism by which P-glycoprotein acts on structurally unrelated groups of chemotherapeutic drugs and has allowed the identification of the protein domain responsible for the common mechanism of transport and recognition of substrate molecules. The function of P-glycoprotein in normal tissues remains intriguing and is discussed in this review.

ISSN:1062-4821    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

The family of Na+- and Cl-dependent, 12 transmembrane domain transporter proteins now includes transporters for neuretransmitter molecules in the brain and for substances important in extraneuronal tissues, including adrenal, kidney, and gut. Transported substrates include monoamine and amino acid neuretransmitters and nonper-turbing osmolytes. A common protein topology is predicted and features intracellular N- and C-termini possessing phosphorylation sites and at least one large extramembranous loop with N-linked glycosylation. Using the rat dopamine transporter as a template, molecular modeling of putative transmembrane domains coupled with amino acid sequence conservation analysis indicates amino acid residues potentially involved in substrate and/or ion recognition. Targeting such residues with site-directed mutagenesis will help clarify substrate and ion binding sites and should facilitate rational design of therapeutics to combat depression, locomotor disorders, and substance abuse.

ISSN:1062-4821    

出版商:OVID    

年代:1993

数据来源: OVID

ISSN:1062-4821    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Approximately 8% to 10% of pregnancies are complicated by hypertension. The disease, whether it first appears during gestation or was present prior to conception, puts both mother and baby at risk. The fetal risks include deathin utero, poor growth, and prematurity. The risks to the mother are more difficult to assess, but intracranial bleeding is the most common cause of death. This review examines some of the physiological changes that occur in normal pregnancy and defines the hypertensive disorders of pregnancy. The recent data regarding pharmacologic and nonpharmacologic therapies for the treatment of hypertension in pregnancy are discussed, and comments as to the prophylaxis of preeclampsia are noted.

ISSN:1062-4821    

出版商:OVID    

年代:1993

数据来源: OVID