Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The high selectivity, low conductance, amiloride-blockable, sodium channel of the mammalian distal nephron (i.e. cortical collecting tubule) is the site of discretionary regulation which allows maintainance of total body sodium balance. In order to understand the physiological events that participate in this regulation, we have used the patch-clamp technique which allows us to measure individual Na+ channel currents and permits access to the cytosolic side of the channel-protein as well as its associated regulatory components. Most of our experiments have utilized the A6 amphibian renal cell line, which when grown on permeable supports is an excellent model for the mammalian distal nephron. Different mechanisms have been examined: (1) regulation by hormonal factors such as Anti-Diuretic Hormone (ADH) and aldosterone, (2) regulation by G-proteins, (3) modulation by protein kinase C (PK-C), and (4) modulation by products of arachidonic acid metabolism. Consistent with noise analysis of tight epithelial tissues, ADH treatment increased the number of active channels in apical membrane patches of A6 cells, without any apparent change in the open probability (Po) of the individual channels. Agents that increased intracellular cAMP mimicked the effects of ADH. In contrast, aldosterone was found to act through a dramatic increase in Po rather than through changes in channel density. Inhibition of methylation by deazaadenosine antagonizes the stimulatory effect of aldosterone. In excised inside-out patches GTP gamma S inhibits channel activity, whereas GDP beta S or pertussis toxin stimulates activity suggesting regulatory control by G-proteins. PK-C has been shown to contribute to 'feed-back inhibition' of apical Na+ conductance in tight epithelia.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Regulation of renal epithelial sodium channels. 133 27

Catecholamines have been shown to activate hypothalamic corticotropin-releasing factor-41 (CRF) synthesis and release. In order to study the mechanisms involved, fetal hypothalamic cells were cultured and CRF release was measured by radioimmunoassay. Norepinephrine (NE) induced CRF release in a dose-dependent manner. Further studies were performed with a protein kinase C inhibitor, H-7(1-(5-isoquinolinesulfonyl)-2-methylpiperazine) and a protein kinase A inhibitor, IP-20. NE-stimulated CRF release was reduced by H-7 (5 and 50 microM) in a dose-dependent fashion, while 5 microM IP-20 resulted in a small but significant inhibition. Pretreatment of the cells for 15 h with 20 and 200 nM 12-O-tetradecanoylphorbol-13-acetate, which down-regulates protein kinase C activity, blocked the release of CRF in response to NE (1 microM), further supporting protein kinase C as a mediator for NE-activated CRF release. Pretreatment with 50 and 500 ng/ml pertussis toxin (15 h) resulted in a dose-dependent inhibition of NE-activated CRF release. Both dexamethasone and aldosterone at the concentrations of 1 microM reduced NE-induced CRF release. These results suggest that CRF can be released from hypothalamic neurons in response to NE through both protein kinase C- and protein kinase A-dependent mechanisms, and that pertussis toxin-sensitive G-proteins are also involved in this response. Furthermore, glucocorticoids and mineralocorticoids can reduce NE-activated CRF release from cultured hypothalamic cells.
 ...
PMID:Mechanisms of norepinephrine mediated corticotropin-releasing factor-41 release from cultured fetal hypothalamic cells. 148 3

The effect of glucocorticoid treatment of DDT1 MF-2 smooth muscle cells on the signaling via two adenosine receptors with opposing actions on cAMP generation was examined. Treatment with dexamethasone caused a dose- and time-dependent increase in the number of adenosine A1 receptors but did not affect the KD or the proportions of receptors in high and low affinity states. The EC50 was 1 nM dexamethasone, and maximal response was achieved after 24 hr. The number of receptors was increased by approximately 50%. Other steroid hormones, including aldosterone, progesterone, testosterone, and estrogen, were much less effective, and addition of the glucocorticoid receptor antagonist RU 486 or the protein synthesis inhibitor cycloheximide prevented the up-regulation, showing that the effect was mediated via a glucocorticoid receptor-specific mechanism that involves protein synthesis. In dexamethasone-treated cells the A1 receptor agonist (-)-N6-phenylisopropyladenosine [(R)-PIA] was 3 times more potent as an inhibitor of cAMP formation induced by isoprenaline than in untreated cells. ADP ribosylation of inhibitory GTP-binding proteins by pertussis toxin completely prevented (R)-PIA from inhibiting cAMP accumulation. A further analysis of the different GTP-binding proteins, including the three Gi subtypes (Gi1, Gi2, and Gi3), revealed no quantitative or qualitative change after dexamethasone treatment. In addition, the adenosine A2 receptors were down-regulated, as indicated by the fact that the ability of the A2 receptor agonist 5'-N-ethylcarboxamidoadenosine to increase cAMP formation was decreased by 20-30% in dexamethasone-treated cells. In summary, we have shown that A1 and A2 receptors on the same cell are differentially regulated by glucocorticoids and that this has functional importance in the regulation of cAMP accumulation.
 ...
PMID:Glucocorticoid receptor activation leads to up-regulation of adenosine A1 receptors and down-regulation of adenosine A2 responses in DDT1 MF-2 smooth muscle cells. 165 51

In a previous study, we have shown that freshly isolated glomerulosa cells possess dopamine (DA) receptors from both DA-1 and DA-2 subclasses, whereas in cultured conditions, cells exhibit dopamine receptors from the DA-1 subclass only. In the present work, we have studied the effect of DA on angiotensin-stimulated glomerulosa cells in these two experimental conditions. Our results demonstrate that in isolated cells, angiotensin II (AT) stimulates inositol phosphate accumulation, calcium influx and steroid secretion. Treatment with pertussis toxin completely blocks AT-stimulated steroid secretion and calcium influx and partially reduces inositol phosphate accumulation. DA alone has no effect on cAMP accumulation. However, in the presence of a specific DA-1 antagonist (SCH 23390), DA reduces intracellular cAMP content. Similarly, DA-like pertussis toxin produces the same inhibitory effects on AT-stimulated cells. The combined influence of DA and pertussis toxin is not additive suggesting that a 'Gi' GTP-binding protein is involved in the DA action. Specific DA antagonists indicate that these inhibitory processes are mediated through the DA-2 receptor subtype. DA may act by decreasing the intracellular calcium concentration since it reduces AT-stimulated Ca2+ influx and that both phospholipase C (PLC) and steroid accumulation are calcium dependent. Yet a direct inhibitory coupling between the DA-2 receptor and PLC may represent a second alternative since DA inhibitory effects are always present when calcium influx is artificially increased or decreased. In cultured cells, we observe an additive effect of DA and AT on aldosterone secretion, which is the result of additive interactions of the second messengers involved, namely cAMP for dopamine and inositol phosphates for angiotensin II. From these studies, we conclude that DA may exert a more versatile effect on aldosterone secretion than previously suspected.
 ...
PMID:Mechanisms involved in the interaction of dopamine with angiotensin II on aldosterone secretion in isolated and cultured rat adrenal glomerulosa cells. 183 52

An adrenal cGMP-stimulated phosphodiesterase (cGS-PDE) has been shown to mediate atrial natriuretic peptide (ANP)-induced reductions in aldosterone secretion and cAMP levels in primary bovine glomerulosa cells. High concentrations of cGS-PDE have been localized to the zona glomerulosa cell layer of the adrenal cortex using biochemical and immunological techniques. Immunoblot analysis using an affinity-purified, isozyme-specific antiserum revealed a single band that comigrated with a purified cGS-PDE (105 kDa) (1) and that was most highly concentrated in the outermost 1-2 mm of the cortex, representing the capsule and zona glomerulosa regions. Greater than 90% of the overall phosphodiesterase activity present in tissue extracts prepared from these regions was immunoprecipitated using a solid-phase monoclonal antibody reagent, indicating the cGS-PDE as the predominant phosphodiesterase isozyme. Immunohistochemical staining experiments of frozen thin sections of intact adrenal tissue revealed that the cGS-PDE present in this region was localized in the glomerulosa cells themselves. The role of this isozyme as a mediator of ANP-induced decreases in intracellular cAMP concentrations and aldosterone production was tested in primary cultures of bovine adrenal glomerulosa cells. In cells stimulated by ACTH, ANP treatment produced dose-dependent reductions in aldosterone secretion and cellular cAMP content over the same concentration range. Increases in aldosterone production elicited by three cell-permeable cAMP derivatives (8-bromo-cAMP, 8-p-chlorophenylthio-cAMP, and N6-2'-O-dibutyryl-cAMP) were antagonized by ANP, indicating a site of action distal to adenylate cyclase for this hormone. Because the relative magnitude of the ANP effect differed depending upon the derivative used, the three derivatives were compared with respect to their relative rates of in vitro hydrolysis by adrenal cGS-PDE. A positive correlation between their rates of hydrolysis and the degree to which the steroidogenic response produced by these derivatives was antagonized by ANP was demonstrated, further suggesting an ANP-induced activation of the cGS-PDE as being responsible for this effect. The possible contribution of an additional pathway mediated by an inhibitory guanine nucleotide binding regulatory protein (Gi) acting on adenylate cyclase was tested by pretreatment of primary glomerulosa cells with pertussis toxin. Levels of pertussis toxin sufficient to inhibit subsequent in vitro ribosylation did not significantly alter the ANP effect on aldosterone production, although a partial reduction in the ANP effect on cAMP levels was observed.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:High concentrations of a cGMP-stimulated phosphodiesterase mediate ANP-induced decreases in cAMP and steroidogenesis in adrenal glomerulosa cells. 184 62

The first step in net active transepithelial transport of sodium in tight epithelia is mediated by the amiloride-blockable sodium channel in the apical membrane. This sodium channel is the primary site for discretionary control of total body sodium and, therefore, investigating its regulatory mechanisms is important to our understanding of the physiology of fluid and electrolyte balance. Because essentially all of the regulatory sites on the channel are on the intracellular surface, patch clamp methods have proven extremely useful in the electrophysiological characterization of the sodium channel by isolating it from other channel proteins in the epithelial membrane and by allowing access to the intracellular surface of the protein. We have examined three different regulatory mechanisms. (1) Inhibition of channel activity by activation of protein kinase C; (2) activation of the channel by agents which activate G-proteins; and (3) modulation of channel kinetics and channel number by mineralocorticoids. Activation of protein kinase C by phorbol esters or synthetic diacylglycerols reduces the open probability of sodium channels. Protein kinase C can be activated in a physiological context by enhancing apical sodium entry. Actions which reduce sodium entry (low luminal sodium concentrations or the apical application of amiloride) increase channel open probability. The link between sodium entry and activation of protein kinase C appears to be mediated by intracellular calcium activity linked to sodium via a sodium/calcium exchange system. Thus, the intracellular sodium concentration is coupled to sodium entry in a negative feedback loop which promotes constant total entry of sodium. Activation of G-proteins by pertussis toxin greatly increases the open probability of sodium channels. Since channels can also be activated by pertussis toxin or GTP gamma S in excised patches, the G-protein appears to be closely linked in the apical membrane to the sodium channel protein itself. The mechanism for activation of this apical G-protein, when most hormonal and transmitter receptors are physically located on the basolateral membrane, is unclear. Mineralocorticoids such as aldosterone have at least two distinct effects. First, as expected, increasing levels of aldosterone increase the density of functional channels detectable in the apical membrane. Second, contrary to expectations, application of aldosterone increases the open probability of sodium channels. Thus aldosterone promotes the functional appearance of new sodium channels and promotes increased sodium entry through both new and pre-existant channels.
 ...
PMID:Regulation of the amiloride-blockable sodium channel from epithelial tissue. 196 46

Progesterone causes natriuresis, an effect largely attributed to displacement of aldosterone from its receptor. The present study, however, demonstrates that progesterone (0.1, 1, and 10 mumol/1, respectively) also causes a rapid, fully reversible depolarization of Madin-Darby canine kidney (MDCK) cells (by 1.3 +/- 0.5, 4.1 +/- 0.7 and 12.3 +/- 1.5 mV, respectively). 17 alpha-Hydroxyprogesterone and dihydroxytestosterone are, by two orders of magnitude, less effective, whereas cholesterol, aldosterone, hydrocortisone, and estradiol (each up to 10 mumol/l) did not significantly alter the potential difference across the cell membrane. The effect of progesterone is blunted by antiprogestogen RU 486 (5 mumol/l). The progesterone-induced depolarization is paralleled by a decrease of potassium selectivity and an increase of cell membrane resistance and is abolished in the presence of the potassium channel blocker barium (10 mmol/l), as well as in the presence of 40 mmol/l potassium in the extracellular fluid. Neither removal of extracellular chloride or bicarbonate nor amiloride, ouabain, or pretreatment with pertussis toxin abolish the depolarizing effect of 5 mumol/l progesterone. In conclusion, acute administration of progesterone depolarizes MDCK cells by decreasing the potassium conductance of the cell membrane.
 ...
PMID:Progesterone inhibits K conductance in plasma membrane of cultured renal epitheloid MDCK cells. 203 30

We have previously shown that vasopressin (VP) induces breakdown of membrane phosphoinositides in adrenal glomerulosa cells. In the present study we demonstrate that the accumulation of inositol phosphates (IP) measured in the presence of arginine vasopressin (AVP) is reduced if the cells are incubated in a calcium-free medium. This effect cannot be accounted for by modification of VP binding, reduction of inositol lipid labeling, or stimulation of inositol, 1,4,5,-triphosphate 5-monophosphatase. It mainly affects phospholipase-C activity, since this enzyme is highly sensitive to calcium. Ionomycine and nifedipine, which, respectively, increase and decrease the intracellular calcium concentration, also, respectively, stimulate and inhibit IP accumulation. In membranes prepared from pertussis toxin (IAP)-treated cells, AVP stimulates inositol monophosphate accumulation to the same extent as in membranes derived from untreated cells. However, in intact cells, IAP decreases the inositol monophosphate accumulation. This decrease probably involves calcium influx, since we show that AVP stimulates a unidirectional calcium influx, which is completely blocked by IAP treatment. In rat adrenal glomerulosa cells, the AVP-stimulated secretion of aldosterone is mainly under the control of calcium, since a full inhibition of its secretion is observed under conditions in which the calcium influxes are completely suppressed despite a sustained accumulation of IP (calcium depletion or IAP treatment). Together, these results signify that VP acts on rat glomerulosa cells by two distinct mechanisms: calcium influx, which is IAP sensitive, and phosphoinositide turnover, which is IAP insensitive.
 ...
PMID:Involvement of distinct G-proteins in the action of vasopressin on rat glomerulosa cells. 210 33

Biochemical studies suggest that stimulation of aldosterone secretion by angiotensin II involves activation of voltage-dependent Ca2+ channels. We used an adrenocortical cell line (Y1) to study the effect of angiotensin II on transmembranous currents. The hormone (1 nM to 1 microM) caused depolarization of the plasma membrane (from -35 to 10 mV) and elicited repetitive action potentials. Using the whole-cell clamp technique, we identified two types of voltage-dependent Ca2+ currents which differed with respect to their threshold potential and time course of inactivation. Angiotensin II (1 nM to 1 microM) stimulated a slowly inactivating Ca2+ current on average up to 1.7-fold whereas a fast inactivating Ca2+ current remained almost unaffected by the hormone. Ca2+ currents were not influenced by forskolin (1 microM) or intracellularly applied cAMP (50 microM). Pretreatment of cells with pertussis toxin abolished the hormonal stimulation of the slowly inactivating Ca2+ current but was without effect on control currents. The toxin ADP-ribosylated a single membranous peptide of 40 kd Mr. An antiserum raised against a synthetic peptide corresponding to a region common to all sequenced alpha-subunits of guanine nucleotide-binding proteins (G-proteins) and an antiserum raised against a peptide corresponding to a region of alpha-subunits of Gi-like G-proteins reacted with membranous 40 kd peptides, whereas an antiserum raised against a synthetic peptide corresponding to a region specific for the alpha-subunit of the G-protein, G0, failed to recognize a peptide in the 39 to 40 kd region.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Angiotensin II-induced stimulation of voltage-dependent Ca2+ currents in an adrenal cortical cell line. 245 9

The effect of glucocorticoids on the dopamine (DA)-mediated cyclic adenosine monophosphate (cAMP) by intact vascular smooth muscle cells (VSMC) was studied in rats. Cultured VSMC were obtained from renal arteries of 14-week-old Wistar-Kyoto rats by explant method. Micromolar concentrations of dexamethasone (DEX) pretreatment for 48 hours potentiated DA-mediated response without any change of affinity constant. However, micromolar concentrations of aldosterone pretreatment for 48 hours had almost no effect on DA-mediated response. The DEX-induced facilitation began at 6 hours and reached maximum at 24 hours after DEX administration in a dose-dependent manner. Inhibitors of protein and RNA synthesis blocked this glucocorticoid effect. The basal activity of adenylate cyclase in DEX-treated cells was twofold higher than that in control cells. Treatment of VSMC with DEX increased cholera toxin-stimulated and forskolin-stimulated adenylate cyclase activity. However, pertussis toxin treatment did not augment or reduce the effect of DEX treatment. These results suggest that glucocorticoids increase DA-mediated cAMP formation by VSMC through glucocorticoid type II receptors and the induction of protein synthesis and that the activation of the catalytic unit may play some role in this facilitation.
 ...
PMID:Glucocorticoids and dopamine-1 receptors on vascular smooth muscle cells. 247 57


1 2 3 4 Next >>