scholarly journals The γ-aminobutyrate/benzodiazepine receptor from pig brain. Enhancement of γ-aminobutyrate-receptor binding by the anaesthetic propanidid

1986 ◽  
Vol 233 (1) ◽  
pp. 259-264 ◽  
Author(s):  
E F Kirkness ◽  
A J Turner
Keyword(s):  
Gaba Receptor ◽  
Benzodiazepine Receptor ◽  
Functional Characteristic ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Gaba Receptor Complex ◽  
Triton X ◽  
Muscimol Binding ◽  
Ic50 Concentration ◽  
Stimulation Of

The binding of [3H]muscimol, a gamma-aminobutyrate (GABA) receptor agonist, to a membrane preparation from pig cerebral cortex was enhanced by the anaesthetic propanidid in a concentration-dependent manner. At 0 degrees C, binding was stimulated to 220% of control values, with 50% stimulation at 60 microM-propanidid. At 37 degrees C, propanidid caused a more powerful stimulation of [3H]muscimol binding (340% of control values). Propanidid (1 mM) exerted little effect on the affinity of muscimol binding (KD approx. 10 nM), but increased the apparent number of high-affinity binding sites in the membrane by 2-fold. Enhancement of [3H]muscimol binding was observed only in the presence of Cl- ions, half-maximal activation being achieved at approx. 40 mM-Cl-. Picrotoxinin inhibited the stimulation of [3H]muscimol binding by propanidid with an IC50 (concentration causing 50% inhibition) value of approx. 25 microM. The enhancement of [3H]muscimol binding by propanidid was not additive with the enhancement produced by secobarbital. Phenobarbital inhibited the effect of propanidid and secobarbital. The GABA receptor was solubilized with Triton X-100 or with Chaps [3-[(3-cholamidopropyl)dimethylammonio]propanesulphonate]. Propanidid and secobarbital did not stimulate the binding of [3H]muscimol after solubilization with Triton X-100. However, the receptor could be solubilized by 5 mM-Chaps with retention of the stimulatory effects of propanidid and secobarbital. Unlike barbiturates, propanidid did not stimulate the binding of [3H]flunitrazepam to membranes. It is suggested that the ability to modulate the [3H]muscimol site of the GABA-receptor complex may be a common and perhaps functional characteristic of general anaesthetics.

Endothelium and mechanical responses of isolated monkey pulmonary veins to histamine

1990 ◽  
Vol 259 (4) ◽  
pp. H1032-H1037 ◽  
Author(s):  
T. Matsuki ◽  
T. Ohhashi
Keyword(s):  
Pulmonary Veins ◽  
Dependent Manner ◽  
High Concentration ◽  
Concentration Dependent Manner ◽  
Mechanical Responses ◽  
Relaxing Factor ◽  
Prostaglandin F2 Alpha ◽  
H2 Receptors ◽  
Endothelium Derived Relaxing Factor ◽  
Stimulation Of

Ring strips of monkey pulmonary veins precontracted with a high concentration of prostaglandin F2 alpha (PGF2 alpha) relaxed in a concentration-dependent manner in response to histamine. Treatment with mepyramine and/or famotidine attenuated the relaxation. 2-Pyridylethylamine (2PEA) and dimaprit caused relaxations in the precontracted preparations, which were inhibited by pretreatment with mepyramine and famotidine, respectively. Removal of endothelium reversed the histamine- and 2PEA-induced relaxations to dose-related contractions. On the other hand, the removal had no effect on the dimaprit-induced relaxations, which were significantly reduced by pretreatment with famotidine. Histamine-induced relaxations in the precontracted strips with endothelium in the presence and absence of famotidine were suppressed or abolished by treatment with methylene blue or hemoglobin but were unaffected by aspirin. It may be concluded that histamine-induced relaxation in monkey pulmonary veins precontracted with PGF2 alpha is mediated by H2-receptors in smooth muscle and H1-receptors in endothelium. Also, stimulation of the endothelial H1-receptors liberates an endothelium-derived relaxing factor.

Differential blockade of agonist- and depolarization-induced 45Ca2+ influx in smooth muscle cells

1989 ◽  
Vol 257 (4) ◽  
pp. C607-C611 ◽  
Author(s):  
A. Wallnofer ◽  
C. Cauvin ◽  
T. W. Lategan ◽  
U. T. Ruegg
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Muscle Cells ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Aortic Smooth Muscle Cells ◽  
Aortic Smooth Muscle ◽  
Gamma S ◽  
Ca2 Channels ◽  
Stimulation Of

ATP stimulated 45Ca2+ influx in rat aortic smooth muscle cells in a concentration-dependent manner (EC50 = 3.6 +/- 0.5 X 10(-7) M). ADP and GTP were less effective than ATP in stimulating 45Ca2+ influx; AMP was weakly active and the adenosine agonist 5'-(N-ethyl-carboxamido)-adenosine (NECA) had no effect. ATP gamma S was about equieffective with ATP, whereas alpha,beta-methylene-ATP (APCPP) did not induce 45Ca2+ influx. Stimulation of 45Ca2+ influx by ATP was not abolished by the dihydropyridine Ca2+ channel antagonist darodipine (PY 108-068), which completely blocked depolarization-induced 45Ca2+ influx. Inorganic cations (La3+, Cd2+, Co2+, Ni2+, Mn2+, and Mg2+) were able to inhibit both agonist- and depolarization-induced 45Ca2+ influx. Cd2+, however, was approximately 20 times more selective in blocking K+-stimulated than agonist-stimulated 45Ca2+ influx. These data indicate that ATP-stimulated Ca2+ influx in rat aortic smooth muscle cells is resistant to darodipine but is reduced by La3+, Cd2+, and other inorganic blockers of Ca2+ channels.

Activation of endothelin ETB receptors increases glomerular cGMP via an L-arginine-dependent pathway

1992 ◽  
Vol 263 (6) ◽  
pp. F1020-F1025 ◽  
Author(s):  
R. M. Edwards ◽  
M. Pullen ◽  
P. Nambi
Keyword(s):  
Nitric Oxide ◽  
Guanylate Cyclase ◽  
Binding Sites ◽  
Soluble Guanylate Cyclase ◽  
Maximum Effect ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
High Affinity ◽  
Dependent Pathway ◽  
Stimulation Of

The effects of endothelins (ET) on guanosine 3',5'-cyclic monophosphate (cGMP) levels in intact rat glomeruli were examined. ET-3 produced a rapid approximately fivefold increase in cGMP levels with the maximum effect occurring at 1 min. The ET-3-induced increase in cGMP accumulation occurred in the absence and presence of 3-isobutyl-1-methylxanthine. ET-1, ET-2, ET-3, and the structurally related toxin, sarafotoxin S6c, all increased glomerular cGMP levels in a concentration-dependent manner and with similar potencies (EC50 approximately 15-30 nM). The L-arginine analogue, N omega-nitro-L-arginine (L-NNA), reduced basal levels of cGMP and also totally inhibited ET-induced increases in cGMP as did methylene blue, an inhibitor of soluble guanylate cyclase. The effect of L-NNA was attenuated by L-arginine but not by D-arginine. The stimulation of cGMP accumulation by ET-3 was dependent on extracellular Ca2+ and was additive to atriopeptin III but not to acetylcholine. The ETA-selective antagonist, BQ 123, had no effect on ET-3-induced formation of cGMP. Glomerular membranes displayed high-affinity (Kd = 130-150 pM) and high-density (approximately 2.0 pmol/mg) binding sites for 125I-ET-1 and 125I-ET-3. ET-1, ET-3, and sarafotoxin S6c displaced 125I-ET-1 binding to glomerular membranes with similar affinities. BQ 123 had no effect on 125I-ET-1 binding. We conclude that ET increases cGMP levels in glomeruli by stimulating the formation of a nitric oxide-like factor that activates soluble guanylate cyclase. This effect of ET appears to be mediated by activation of ETB receptors and may serve to modulate the contractile effects of ET.

Stimulation of renin secretion by ethacrynic acid is independent of Na(+)-K(+)-2Cl- cotransport

1990 ◽  
Vol 259 (4) ◽  
pp. F539-F544 ◽  
Author(s):  
C. S. Park ◽  
P. S. Doh ◽  
R. E. Carraway ◽  
G. G. Chung ◽  
J. C. Fray ◽  
...  
Keyword(s):  
Loop Diuretic ◽  
Ethacrynic Acid ◽  
Inhibitory Effect ◽  
Renin Secretion ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Specific Membrane ◽  
Cortical Slices ◽  
Stimulation Of

This study investigated the cellular mechanism of stimulation of renin secretion by the loop diuretic ethacrynic acid (EA) in rabbit renal cortical slices. The diuretic rapidly stimulated renin secretion reversibly and in a concentration-dependent manner. The stimulation was independent of the presence of Na+, Cl-, Ca2+, or other loop diuretics (furosemide and bumetanide) in the incubation media, suggesting that the stimulation in vitro was not dependent on the inhibitory effect of the diuretic on Na(+)-K(+)-2Cl-cotransport. The findings do not support the macula densa hypothesis. The stimulation by the diuretic was prevented and reversed by thiols such as cysteine and dithiothreitol, which also prevented and reversed the stimulation of renin secretion by the nondiuretic sulfhydryl reagent P-chloromercuriphenyl-sulfonate (PCMPS). These results suggest that EA stimulates renin secretion in vitro via reversible chemical reactions with specific membrane sulfhydryl groups that may have no functional role in the Na(+)-K(+)-2Cl- cotransport.

Endothelin activation of phospholipase D: dual modulation by protein kinase C and Ca2+

1993 ◽  
Vol 264 (5) ◽  
pp. F845-F853
Author(s):  
M. M. Friedlaender ◽  
D. Jain ◽  
Z. Ahmed ◽  
D. Hart ◽  
R. L. Barnett ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Phospholipase D ◽  
Intracellular Signaling ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Kinase C ◽  
Eta Receptor ◽  
Ca2 Channels ◽  
Stimulation Of

Previous work from this laboratory has identified an endothelin (ET) type A (ETA) receptor on cultured rat renal medullary interstitial cells (RMIC), coupled to phosphatidylinositol-specific phospholipase C (PI-PLC), dihydropyridine-insensitive receptor-operated Ca2+ channels, and phospholipase A2. The current studies explored a role for ET stimulation of phosphatidylcholine-specific phospholipase D (PC-PLD) in intracellular signaling of this cell type. ET stimulated PLD activation, as measured by phosphatidic acid (PA) or phosphatidylethanol (PEt) accumulation, in a time- and concentration-dependent manner. Inhibition of diacylglycerol (DAG) kinase by ethylene glycol dioctanoate or 6-(2)4-[(4-fluorophenyl)-phenylmethylene]-1-piperadinyl]ethy l-7-methyl-5H - thiaxolo-[3,2-alpyrimidin]-5-one (R 59022) failed to blunt PA accumulation, indicating that PLD, and not DAG, was the source of PA. Inhibition of PA phosphohydrolase (PAP) by propranolol increased late accumulation of PA, suggesting that the prevailing metabolic flow was in the direction of PA to DAG. Phorbol 12-myristate 13-acetate (PMA) augmented ET-evoked PEt accumulation, whereas downregulation of protein kinase C (PKC) obviated agonist-induced PEt production. PMA augmentation of PLD activity proceeded independent of cytosolic free Ca2+ concentration. Ca2+ derived from either intracellular or extracellular sources enhanced ET-related PEt accumulation but was without effect in PKC-downregulated cells. Collectively, these observations indicate that ET stimulates PLD production in RMIC. PKC is the major regulator of this process, with Ca2+ playing a secondary, modulatory role. In addition, these data suggest that PC-PLD is coupled to the ETA receptor.

Na regulates growth of kidney epithelial cells induced by lowering extracellular K concentration

1984 ◽  
Vol 247 (5) ◽  
pp. C321-C326 ◽  
Author(s):  
M. M. Walsh-Reitz ◽  
H. N. Aithal ◽  
F. G. Toback
Keyword(s):  
Cell Growth ◽  
Epithelial Cells ◽  
Dependent Manner ◽  
Deficient Diet ◽  
Critical Determinant ◽  
Concentration Dependent Manner ◽  
Kidney Epithelial Cells ◽  
K Concentration ◽  
Low K ◽  
Stimulation Of

Accelerated kidney growth and increased tissue Na content have been observed in rats fed a K-deficient diet. These observations suggest that enhanced Na influx could mediate renal growth, a hypothesis that was tested in cultures of kidney epithelial cells of the BSC-1 line. Reduction of the K concentration in the culture medium from 5.4 to 3.2 mM augmented cell growth and induced a transient increase in the cellular content of Na and a decrease in that of K. That low-K-induced growth was Na dependent was shown by decreasing the medium Na concentration from 155 to 150 mM, which abolished the increases in both growth and cell Na content in a concentration-dependent manner. The stimulation of glyceraldehyde-3-phosphate dehydrogenase (G3PD) activity that occurs in cells exposed to low-K medium for 1 h was similarly prevented by decreasing the medium Na concentration. Thus decreased availability of extracellular Na prevented the increase in cell Na content, stimulation of G3PD activity, and accelerated growth induced by low-K medium. The hypothesis was also tested by adding vasopressin to cultures of BSC-1 cells exposed to low-K medium; the hormone prevented the increments in cell Na content, G3PD activity, and growth to the same extent as did decreased availability of extracellular Na. These results are consistent with the interpretation that transient accumulation of Na is a critical determinant of the initiation of kidney epithelial cell growth.

scholarly journals Stimulation of plasmin activity by oleic acid

1992 ◽  
Vol 282 (3) ◽  
pp. 863-866 ◽  
Author(s):  
A A R Higazi ◽  
Z Finci-Yeheskel ◽  
A A R Samara ◽  
R Aziza ◽  
M Mayer
Keyword(s):  
Oleic Acid ◽  
Binding Sites ◽  
Maximal Effect ◽  
Dependent Manner ◽  
Plasmin Activity ◽  
Concentration Dependent Manner ◽  
Acid Analogue ◽  
Kinetic Pattern ◽  
Fold Stimulation ◽  
Stimulation Of

The amidolytic activity of plasmin with the chromogenic substrate H-D-valyl-L-leucyl-L-lysine p-nitroanilide (S-2251) is stimulated by oleic acid in a dose-dependent and saturable fashion. The activity of plasmin on S-2251 in the presence of oleic acid followed a sigmoidal kinetic pattern, with an almost 4-fold stimulation of activity at 60 microM-oleic acid. Half-maximal stimulation occurred at an oleic acid level of 19.5 microM. The amino acid analogue 6-aminohexanoic acid (AHA), which is known to bind to lysine-binding sites in plasmin, suppressed the stimulatory effect of oleic acid in a concentration-dependent manner; at 0.3 mM-AHA, about 70% of the oleic acid-dependent enhancement of plasmin activity was abolished. The l/v versus 1/[S] plot for plasmin changed in the presence of oleic acid from a linear to a non-linear curve, suggesting positive co-operativity. 14C-labelled oleic acid bound to plasmin, and the bound ligand was displaced by an excess of unlabelled oleic acid. Oleic acid also produced a marked (40-fold) stimulation of the plasminogen-dependent cleavage of S-2251 by urokinase. A half-maximal effect on plasminogen activation was obtained at 40 microM-oleic acid. The present findings suggest that the ability of oleic acid to stimulate plasmin activity and to enhance the conversion of plasminogen to plasmin depends on the interaction of oleic acid with specific lysine-binding sites in plasmin.

scholarly journals Regulation of the electrogenic H+ channel in the plasma membrane of neutrophils: possible role of phospholipase A2, internal and external protons

1993 ◽  
Vol 292 (2) ◽  
pp. 445-450 ◽  
Author(s):  
A Kapus ◽  
K Suszták ◽  
E Ligeti
Keyword(s):  
Plasma Membrane ◽  
Phospholipase A2 ◽  
Neutrophil Granulocytes ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Conducting Pathway ◽  
External Ph ◽  
Force Relationship ◽  
Stimulation Of

Possible factors regulating the opening of and the rate of H+ flux through a recently described, Cd(2+)-sensitive, phorbol ester- and arachidonic acid (AA)-activatable H(+)-conducting pathway in the plasma membrane of neutrophil granulocytes were investigated. (1) The phospholipase A2 blocker p-bromophenacyl bromide (BPB) inhibited the phorbol 12-myristate 13-acetate (PMA)-induced activation of this channel in a concentration-dependent manner (IC50, 4 microM). (2) Neither BPB nor the protein kinase C (PKC) inhibitor staurosporine influenced the AA-elicited stimulation of this route. (3) Intracellular acidification (cytoplasmic pH below 6.9) itself is capable of activating an electrogenic, Cd(2+)-sensitive H+ efflux indicating that protons can open up this route in the absence of any other stimulator. (4) PMA significantly decreases the intracellular H+ concentration ([H+]i) threshold for the opening of the channel, thus providing a conductive state at resting pH values, and elevates the rate of H+ efflux at any [H+]i. (5) Changes in external pH also modify the operation of the channel: above an extracellular pH (pH(o)) value of 7.4, the H(+)-flux/driving force relationship is approx. 5-fold greater than below this value. Our results suggest a multifactorial regulation of the electrogenic H+ channel: most probably PKC activates the channel indirectly, via stimulation of phospholipase A2 that subsequently liberates AA. In addition to this, the channel conductance seems to be promoted by internal H+ and inhibited by external H+.

scholarly journals Rat surfactant protein D enhances the production of oxygen radicals by rat alveolar macrophages

1992 ◽  
Vol 286 (1) ◽  
pp. 5-8 ◽  
Author(s):  
J F Van Iwaarden ◽  
H Shimizu ◽  
P H M Van Golde ◽  
D R Voelker ◽  
L M G Van Golde
Keyword(s):  
Alveolar Macrophages ◽  
Oxygen Radicals ◽  
Protein A ◽  
Surfactant Protein ◽  
Surfactant Protein A ◽  
Surfactant Protein D ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Oxygen Radical Production ◽  
Stimulation Of

Rat surfactant protein D (SP-D) was shown to enhance the production of oxygen radicals by rat alveolar macrophages. This enhancement, which was determined by a lucigenin-dependent chemiluminescence assay, was maximal after 18 min at an SP-D concentration of 0.2 micrograms/ml. Surfactant lipids did not influence the stimulation of alveolar macrophages by SP-D, whereas the oxygen-radical production of these cells induced by surfactant protein A was inhibited by the lipids in a concentration-dependent manner.

Tyrosine kinase inhibitors block the glucocorticoid stimulation of prostaglandin endoperoxide H synthase expression in amnion cells

1999 ◽  
Vol 77 (2) ◽  
pp. 138-142 ◽  
Author(s):  
Tamas Zakar ◽  
Jane E Mijovic ◽  
Damyanti Bhardwaj ◽  
David M Olson
Keyword(s):  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Kinase Inhibitors ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Prostaglandin Endoperoxide ◽  
Herbimycin A ◽  
Cell Extracts ◽  
Endoperoxide H Synthase ◽  
Stimulation Of

Human amnion cells in primary culture respond to glucocorticoids in a characteristic fashion by the increased expression of the inducible prostaglandin endoperoxide H synthase isoenzyme, PGHS-2. Since PGHS-2 induction by agonists generally involves tyrosine kinases, we examined the possibility that the glucocorticoid stimulation of PGHS-2 in the amnion cells is tyrosine kinase dependent. PGHS-2 expression was stimulated in confluent, serum-starved amnion cells with dexamethasone, and the effect of the tyrosine kinase inhibitors herbimycin A and tyrphostins AG126, AG1288, and A1 on enzyme activity induction was determined. All four inhibitors blocked the increase of PGHS activity in a concentration-dependent manner with IC50 values of 0.077 ± 0.05, 15.38 ± 5.14, 20.91 ± 3.1, and 29.77 ± 8.21 µM, respectively (mean ± SE, n = 4). Dexamethasone increased (approximately twofold) the tyrosine phosphorylation of 120-, 110-, and 77-kDa proteins in cell extracts, and herbimycin A selectively blocked the phosphorylation of the 110-kDa phosphoprotein. The stimulation of the steady-state level of PGHS-2 mRNA by dexamethasone was also inhibited by herbimycin A. These results suggest that glucocorticoids induce PGHS-2 expression in amnion cells with the involvement of tyrosine kinase(s). The role of tyrosine kinase dependent mechanisms in the control of amnion cell responsiveness to corticosteroids remains to be established.Key words: amnion, glucocorticoid, tyrosine kinase, prostaglandin H synthase.

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