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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although the pattern of expression of various sodium channel alpha- and beta-subunits changes as development proceeds, the mechanisms that control the expression of these subunits are not yet understood. To study the role of nerve growth factor (NGF) in modulating the expression of sodium channel subunits, we used in situ hybridization cytochemistry to examine the distribution of sodium channel alpha- and beta 1-subunit mRNAs in embryonic day 16 (E16) dorsal root ganglia (DRG) neurons cultured in the absence or presence of NGE. At 4 days in vitro in the absence of NGF, sodium channel alpha-subunit II mRNA was expressed at low-to-moderate levels in DRG neurons, but the transcripts for sodium channel alpha-subunits I, III and NaG and beta 1-subunit were not detectable. In the presence of NGF, DRG neurons expressed low-to-moderate levels of sodium channel alpha-I, high levels of alpha-II and low levels of alpha-III; NaG mRNA was not detectable. Sodium channel beta 1 mRNA was up-regulated and was expressed at high levels in DRG neurons in NGF-containing media. These observations demonstrate that the NGF exerts a differential up-regulation of sodium channel alpha- and beta-subunit mRNAs in DRG neurons derived from E16 embryos.
Brain Res Mol Brain Res 1995 May
PMID:Differential up-regulation of sodium channel alpha- and beta 1-subunit mRNAs in cultured embryonic DRG neurons following exposure to NGF. 760 49

1. While intracellular calcium concentrations are closely regulated, two types of ion channels in neurons allow calcium influx: both voltage-activated and NMDA-activated channels are significantly permeable to calcium. In this study we compare the effects of lead (Pb2+) on currents carried through voltage-activated calcium channels and NMDA-activated channels. 2. Pb2+ reduces voltage-activated calcium channel currents elicited by a voltage jump from -80 to 0 mV at 0.1 to 1 microM, with an IC50 of 0.64 microM and a Hill slope of 1.22. This effect was partially reversible and not voltage dependent. Sodium and potassium currents were relatively unaffected at Pb2+ concentrations sufficient to block calcium channel currents by more than 80%. Pb2+ is, thus, a potent, reversible and selective blocker of voltage-dependent calcium channel currents. 3. A fast reversible and slow irreversible blocking action of Pb2+ was found on NMDA-activated currents. When Pb2+ was applied simultaneously with aspartate and glycine (Asp/Gly), the inward currents were rapidly and reversibly reduced in a dose-dependent manner with a minimum effective concentration below 2 microM and a total blockade (> 80%) with 100 microM Pb2+. The IC50 was approximately 45 microM and the Hill coefficient 1.1. Preincubation with 50 microM Pb2+ resulted in a greater reduction in the response to Asp/Gly/Pb2+. This effect was reversed within 2 to 5 sec of wash. The lack of voltage dependence suggests that Pb2+ does not block the channel but rather alters the binding of agonists. Prolonged superfusion of a cell with the Asp/Gly/Pb(2+)-containing external solution resulted in a slow and irreversible decrease in the Asp/Gly activated current.(ABSTRACT TRUNCATED AT 250 WORDS)
Cell Mol Neurobiol 1994 Dec
PMID:Pb2+ reduces voltage- and N-methyl-D-aspartate (NMDA)-activated calcium channel currents. 764 Dec 31

The cellular localization of rat brain sodium channel alpha-subunit mRNAs I, II and III in the central nervous system (CNS) was examined by non-isotope in situ hybridization cytochemistry utilizing two independent sets of isoform-specific RNA probes, one set recognizing sodium channel isoforms in the coding region and the other in the non-coding region of the sodium channel messages. The independent sets of probes demonstrated qualitatively similar patterns of sodium channel mRNA expression. In the hippocampus, sodium channel mRNA I was very weakly expressed in the pyramidal layer and in the granular layer of the dentate gyrus; in contrast, sodium channel mRNA II was strongly expressed by neurons in these regions. Sodium channel mRNA III exhibited low-to-moderate expression in some neurons of the pyramidal layer of the hippocampus and granular layer of the dentate gyrus, and was not detectable in others. In the cerebellum, sodium channel mRNA I was moderately expressed in some Purkinje cells, weakly expressed in scattered cells in the molecular layer and negligibly expressed in the granular layer. Sodium channel mRNA II was strongly expressed in Purkinje and granule cells, and was moderately expressed in some cells in the molecular layer. Sodium channel mRNA III was generally not detectable in the cerebellum. In the spinal cord, motor neurons and scattered neurons throughout the gray matter exhibited moderate-to-strong expression of both sodium channel mRNA I and II. A population of cells in the spinal zone of Lissauer showed heavy expression of mRNA II, but not mRNA I. Sodium channel mRNA III was not detectable in spinal cord neurons. These observations are consistent with a general regional distribution of sodium channel message isoforms, with mRNA II being preferentially expressed in rostral regions of the CNS and mRNA I in caudal regions. However, the results also indicate that different cell types, within a given region, display different patterns of sodium channel mRNA expression. Moreover, these data suggest that individual neurons may express multiple forms of sodium channel mRNA.
Brain Res Mol Brain Res 1994 Mar
PMID:Sodium channel mRNAs I, II and III in the CNS: cell-specific expression. 801 85

The expression of rat brain sodium channel alpha-subunit mRNAs I, II and III and a putative glial cell-specific sodium channel (NaG) mRNA was examined in cultured astrocytes from P-0 rat spinal cord by RNA blot hybridization and by non-isotope in situ hybridization cytochemistry utilizing two independent sets of isoform-specific RNA probes. Sodium channel mRNA I was not detectable in the cultured astrocytes by RNA blot or in situ hybridization. Sodium channel mRNA II showed negligible-to-low levels of expression in flat, fibroblast-like and 'pancake' astrocytes at 4 days in vitro (div), while stellate, process-bearing astrocytes exhibited low-to-moderate levels of mRNA II expression. At 7 div, mRNA II expression ranged from low-to-moderate in flat astrocytes and was moderately high in most process-bearing astrocytes. In RNA blots, a weak band was observed at 9.5 kb. Sodium channel mRNA III expression was negligible in flat astrocytes and was detectable in low-to moderate levels in stellate astrocytes beginning at 4 div; by 7 div, mRNA III was detectable in low levels in flat astrocytes and low-to-moderate levels in stellate astrocytes. RNA blots showed two bands of nearly equal intensity, one at 9.0 kb and one at 7.2 kb. NaG mRNA showed increased expression with time in culture, being detectable in flat and stellate astrocytes at 4 div and becoming very prominent in flat astrocytes at extended times in culture. In RNA blots of cultured astrocytes at 7 div, a strong hybridizing signal with the NaG probe was observed. These observations demonstrate that flat and stellate astrocytes cultured from rat spinal cord express rat brain sodium channel mRNA II and III, and NaG, and suggest that astrocytes in vitro may co-express multiple forms of sodium channel mRNA.
Brain Res Mol Brain Res 1994 May
PMID:Sodium channel mRNAs in cultured spinal cord astrocytes: in situ hybridization in identified cell types. 805 80

The changes of intracellular pH (pHi) produced by hypoxia in sheep heart Purkinje fibres were studied using liquid ion exchanger-filled microelectrodes. A decrease of temperature from 35 degrees C to 22 degrees C caused an alkalinization of 0.3 pH units. Hypoxia (partial pressure of oxygen < 10 mm Hg) for 20 min induced an acidification of 0.26 +/- 0.18 units (n = 14) at 35 degrees C. The hypoxia-induced acidification at 22 degrees C was smaller than that at 35 degrees C by approximately 65%. Increasing the buffering capacity of the cells decreased the hypoxic acidification. This could be achieved either by use of high extracellular HEPES concentrations (40 mM) or by the use of bicarbonate buffers. Sodium cinnamate (5 mM) increased the hypoxic acidification and slowed the pHi recovery on reintroduction of oxygen, implying an importance role for lactate flux in pH regulation during hypoxia.
J Mol Cell Cardiol 1994 Apr
PMID:Hypoxia-induced intracellular acidification in isolated sheep heart Purkinje fibres and the effects of temperature. 807 4

Sodium ions have been shown to reduce the binding of agonists to a number of G protein-linked receptors. They are believed to do so by interacting with aspartate residues in the second membrane-spanning region of these receptors to cause G protein uncoupling, resulting in a diminished affinity of the receptors for agonists. To investigate Na+ regulation of agonist binding to somatostatin receptors, Na+ was tested for its effect on the binding of agonists to cloned somatostatin receptor type 1 (SSTR1) and somatostatin receptor type 2 (SSTR2) stably expressed in Chinese hamster ovary cells. Na+ reduced agonist binding to SSTR2 but not to SSTR1. Because high affinity agonist binding to SSTR1 does not depend on G protein coupling but agonist binding to SSTR2 is reduced by guanosine-5'-(beta, gamma-imido)triphosphate and pertussis toxin treatment, the selective Na+ effect on SSTR2 is consistent with previous findings with other receptors showing that Na+ uncouples receptors from G proteins, thereby reducing the affinity of the receptors for agonists. Conversion of Asp89 to Asn89 in SSTR2 resulted in a mutant receptor whose affinity for agonists was not altered by Na+, indicating that Asp89 is involved in mediating the effects of Na+ on agonist binding to SSTR2. However, the affinities of the mutant and wild-type receptors for somatostatin were the same, and both guanosine-5'-O-(gamma-thio)triphosphate and pertussis toxin treatment reduced agonist binding to the mutant and wild-type receptors. These findings differ from the results of similar mutagenesis studies on other G protein-linked receptors, in that the mutant and wild-type SSTR2 forms associate with G proteins in similar ways. These results indicate that Asp89 acts in a novel manner to regulate agonist binding and G protein interaction with SSTR2.
Mol Pharmacol 1993 Aug
PMID:Mutation of an aspartate at residue 89 in somatostatin receptor subtype 2 prevents Na+ regulation of agonist binding but does not alter receptor-G protein association. 810 84

In a previous study, we showed that binding of FSH by cultured rat Sertoli cells significantly inhibited basal levels of Na+/Ca2+ exchange. Similar inhibition was observed when proteoliposomes enriched with bovine calf testis follicle-stimulating hormone (FSH) receptors were stimulated with FSH. In the present study, we screened a series of overlapping synthetic peptide amides, representing the entire primary structure of the beta-subunit of hFSH, for their effects on sodium-dependent calcium uptake (as 45Ca2+) by monolayer cultures of Sertoli cells from immature rats. hFSH-beta-(33-53), previously identified as a receptor binding region of hFSH-beta-subunit, significantly (P < 0.05) inhibited Na+/Ca2+ exchange. A tetrapeptide [TRDL, hFSH-beta-(34-37)] contained within this sequence, was observed to be equally as active as hFSH-beta-(33-53) at 200 microM, suggesting that the regulatory effect of hFSH-beta-(33-53) on sodium-dependent 45Ca2+ influx was due to residues 34-37. hFSH-beta-(81-95) also inhibited Na(+)-dependent calcium influx, although to a lesser extent than hFSH-beta-(33-53) or hFSH-beta-(34-37). Sodium-dependent 45Ca2+ entry into Sertoli cells was enhanced in a concentration-related manner when extracellular sodium was replaced by equimolar concentrations (up to 135 mM) of choline chloride. hFSH-beta-(34-37) significantly reduced basal uptake of 45Ca2+ in choline-containing buffer, but was without effect in buffer containing 135 mM NaCl.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Cell Endocrinol 1993 Oct
PMID:A tetrapeptide within a receptor-binding region of human follicle-stimulating hormone beta-subunit, hFSH-beta-(34-37), regulates sodium-calcium exchange in Sertoli cells. 827 34

Amino acid transport is facilitated by specific transporters within the plasma membrane of the cell. In mouse oocytes and cleavage-stage conceptus Na(+)-dependent L-alanine and L-leucine transport are nearly undetectable. Sodium-dependent transport via system B0,+ in the mouse conceptus increases greatly between the 8-cell and blastocyst stages. By contrast, data presented here for the pig show that L-alanine and L-leucine transport is mainly Na(+)-dependent in the oocyte; this Na(+)-dependent component of transport becomes undetectable by the blastocyst stage. The Na(+)-dependent component of transport in oocytes is inhibited by BCH (2-aminoendo-bicyclo[2.2.1] hexane-2-carboxylic acid) and L-lysine and thus could be a form of system B0,+. In both oocytes and blastocysts Na(+)-independent L-leucine transport is inhibited by BCH, which is consistent with the presence of system L. The dramatic decrease in Na(+)-dependent amino acid transport activity could occur in pig conceptuses in association with the onset of RNA synthesis during the 4-cell stage. Regardless of the precise time during development at which it occurs, however, this dramatic, developmentally regulated decrease in Na(+)-dependent alanine and leucine transport activity contrasts sharply with the large increase in Na(+)-dependent system B0,+ activity that occurs during preimplantation development of murine conceptuses. Elucidation of the molecular mechanisms by which these changes occur should contribute to an understanding of regulation of gene expression during early development.
Mol Reprod Dev 1993 Mar
PMID:Alanine and leucine transport in unfertilized pig oocytes and early blastocysts. 847 Dec 46

The biosynthesis of aldosterone in the adrenal zona glomerulosa is influenced by a number of factors of which the main physiological regulator is the octapeptide, angiotensin II (AII). Sodium restriction increases plasma aldosterone, adrenal glomerulosa AII receptors and the activity of enzymes of the early and late aldosterone biosynthetic pathway. The effects of sodium restriction are mimicked by prolonged administration of low doses of AII, and prevented by blockade of AII formation using converting enzyme inhibitors, indicating that the effects of sodium restriction are mediated by AII. However, the adrenal glomerulotrophic actions of AII are impaired in rats on high sodium diet indicating that other factors are modulating the effects of AII in these conditions. A number of factors are known to influence aldosterone secretion, several of which have been shown to preferentially modulate the effect of AII. While the stimulatory effect of AII is potentiated by serotonin or increases in extracellular potassium, it is inhibited by dopamine, somatostatin and atrial natriuretic peptide. Future investigations will be important to understand the relative role of the individual regulators in the physiological control of adrenal sensitivity to AII, and how activation of various intracellular messenger systems results in changes in activity of the enzymes of the aldosterone biosynthetic pathway.
J Steroid Biochem Mol Biol 1993 Apr
PMID:Factors controlling steroid biosynthesis in the zona glomerulosa of the adrenal. 848 39

The effects of sodium phenobarbital and sodium barbital on the activity of the particulate and cytosolic 5 alpha-dihydroprogesterone 3 alpha-hydroxysteroid oxidoreductases (3 alpha-HSORs) of female rat anterior pituitary were investigated. By altering the 3 alpha-HSOR catalyzed conversion of 5 alpha-dihydroprogesterone (5 alpha-DHP) to 3 alpha,5 alpha-tetrahydroprogesterone (3 alpha,5 alpha-THP), these barbiturates could influence the in situ production of 3 alpha,5 alpha-THP. 3 alpha,5 alpha-THP has potent barbiturate-like effects on brain GABAA receptors. Both phenobarbital and 3 alpha,5 alpha-THP can affect gonadotropin release in female rats. In vitro incubations of each 3 alpha-HSOR activity were assayed in the presence of sodium phenobarbital (0.1 to 10.0 mM) or sodium barbital (1.0 to 10.0 mM). Since both 3 alpha-HSOR activities catalyze the reversible oxidoreduction of 5 alpha-DHP and 3 alpha,5 alpha-THP, we examined the effect of these barbiturates not only on the conversion of 5 alpha-DHP to 3 alpha,5 alpha-THP (reductive reaction) but also on the "back conversion" of 3 alpha,5 alpha-THP to 5 alpha-DHP (oxidative reaction). The results indicate that both phenobarbital and, to a lesser extent barbital, significantly affected the activities of the two 3 alpha-HSORs in both reductive and oxidative directions. In the reductive direction, phenobarbital inhibited the activity (33%) of both cytosolic and particulate enzymes which would presumably decrease the levels of 3 alpha,5 alpha-THP. In the oxidative direction, a pattern of stimulation was observed (20 to 100%). Thus, this stimulatory effect on the oxidative conversion of 3 alpha,5 alpha-THP to 5 alpha-DHP, which would presumably also decrease 3 alpha,5 alpha-THP levels, appears correlated with the inhibitory effect of these barbiturates on the reductive conversion of 5 alpha-DHP to 3 alpha,5 alpha-THP. Sodium barbital exhibited somewhat similar effects. These changes suggest that barbiturates can lower 3 alpha,5 alpha-THP levels in the anterior pituitary. The results also suggest the possibility that lowered 3 alpha,5 alpha-THP levels may be involved, at least in part, in the reduction of gonadotropin release by barbiturates.
J Steroid Biochem Mol Biol 1993 Apr
PMID:Barbiturates modulate the activity of the pituitary 3 alpha-hydroxysteroid oxidoreductases and inhibit their production of 3 alpha,5 alpha-tetrahydroprogesterone. 849 36


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