Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Onium Compounds”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 937 records · Page 52Linked to original sources
PubMed1993

Effects of chronic nicotine treatment on the accumulation of [3H]tetraphenylphosphonium by cerebral cortical synaptosomes.

Chronic exposure of rats to nicotine increases the number of [3H]nicotine binding sites in the brain; however, it is not clear whether nicotinic cholinergic receptor function is altered as well. In this study, we have used [3H]tetraphenylphosphonium as a probe of synaptosomal membrane potential to investigate whether exposure to nicotine in vivo alters the ability of cerebral cortical synaptosomes to maintain a potential difference and to depolarize in response to in vitro nicotine. Treatment of rats for 14 days with 0.475 mg of nicotine base/day via subcutaneously implanted minipumps resulted in a decrease in the synaptosomal accumulation of [3H]tetraphenylphosphonium in physiological buffer, corresponding to a decrease in estimated membrane potential from -55 mV to -50 mV. The onset of the decrease in membrane potential occurred after 7 days of in vivo nicotine treatment and was significantly correlated with an increase in [3H]nicotine binding to cerebral cortical synaptosomal (P2) membranes. Nicotine, at in vitro concentrations of 3-1,000 microM, decreased [3H]tetraphenylphosphonium accumulation in cerebral cortical synaptosomes from control animals. When compared to accumulation in buffer alone, in vitro nicotine and other nicotinic agonists did not significantly decrease [3H]tetraphenylphosphonium accumulation in cerebral cortical synaptosomes prepared from rats treated with nicotine in vivo. These studies provide evidence that chronic treatment with nicotine results in an average lower membrane potential in cerebral cortical synaptosomes and in functional down-regulation of the depolarization response to nicotinic cholinergic receptor stimulation.

Animals↗
PubMed1991

Characterization in rat aorta of the binding sites responsible for blockade of noradrenaline-evoked calcium entry by nisoldipine.

1. The effectiveness of the calcium antagonist, 1,4-dihydropyridine nisoldipine, as an inhibitor of contraction and 45Ca entry evoked by noradrenaline in rat aorta has been investigated and correlated with binding characteristics in intact artery. 2. Contractions evoked by noradrenaline were concentration-dependently depressed by nisoldipine (0.3-300 nM). About 60% of the response was resistant to inhibition, while KCl-induced contractions could be completely blocked. Noradrenaline-induced contractions were also less sensitive to nisoldipine inhibition than were KCl-induced contractions. 3. Preincubation of the aorta with nisoldipine in high KCl depolarizing solution increased the inhibition of the contraction evoked by a short application of noradrenaline or KCl to a similar extent. 4. The inhibition by nisoldipine of 45Ca influx evoked either by KCl depolarizing solution or by noradrenaline correlated well with the inhibition of the contractile responses. However, while KCl-stimulated 45Ca influx was totally abolished by nisoldipine (300 nM), 38% of the noradrenaline-stimulated 45Ca influx was resistant to inhibition by nisoldipine (300 nM). 5. The study of [3H]-(+)-PN 200-10 ([3H]-(+)-isradipine) binding in intact aorta showed the presence of a homogeneous population of specific binding sites. KD values were dependent on the KCl concentration in the bath while Bmax was unaffected. Binding of [3H]-(+)-isradipine was also increased in tissue exposed to noradrenaline; in the presence of 10(-5) M noradrenaline, binding parameters of [3H]-(+)-isradipine were close to the values obtained in aorta bathed in 20 mM KCl solution. 6. Displacement of [3H]-(+)-isradipine specific binding by nisoldipine was determined in segments of mesenteric artery and of aorta. The potency of nisoldipine was dependent on the incubation conditions applied to the vessel, as follows: KCl (100 mM) depolarizing solution greater than noradrenaline (10(-5) M) = KCl (25 mM) solution greater than physiological solution. The Ki value measured in aorta exposed to noradrenaline (10(-5) M) was close to the IC50 value of nisoldipine on the noradrenaline-evoked contraction. 7. The membrane potential value of rat aorta was estimated by the distribution of [3H]-tetraphenylphosphonium bromide ([3H]-TPP+), [3H]-TPP+ uptake concentration-dependently decreased when the KCl concentration in the bath was increased from 5.9 to 130 mM. Noradrenaline also concentration-dependently decreased [3H]-TPP+ uptake; the maximum effect (1-10 microns noradrenaline) was comparable in amplitude to the effect of 25 mM KCl solution. 8. It is concluded that in rat aorta, noradrenaline activates voltage-operated calcium channels that contain the specific, voltage-sensitive binding sites for calcium antagonistic dihydropyridines. The existence of a fraction of noradrenaline-stimulated '"Ca entry that is resistant to nisoldipine blockade suggests that another Ca2 + entry pathway is also opened by the agonist.

Animals↗
PubMed1993

Halothane inhibits the pressor effect of diphenyleneiodonium.

1. We have recently found that diphenyleneiodonium (DPI), a novel inhibitor of nitric oxide (NO) synthase, causes pressor and tachycardic responses in pentobarbitone- but not halothane-anaesthetized rats. The present study investigated the mechanism by which halothane suppresses the pressor response of DPI. The effects of halothane on the pressor response of DPI were also compared with those of other anaesthetic agents. 2. In conscious rats, i.v. bolus injections of DPI (0.025- 1.6 mg kg-1) caused dose-dependent increases in mean arterial pressure (MAP), with ED90 of 0.07 +/- 0.01 mg kg-1 and maximal rise of MAP (Emax) of 59 +/- 2 mmHg. While ketamine potentiated Emax without altering the ED50 and pentobarbitone increased the ED50 without changing Emax of the pressor response to DPI, chloralose, urethane and ethanol displaced the curve to the right and potentiated Emax. In contrast, halothane (0.5-1.25%) dose-dependently and non-competitively reduced the pressor responses to DPI. 3. Intravenous bolus injection of a single dose of DPI (1.6 mg kg-1) caused immediate and large increases in plasma noradrenaline and adrenaline, as well as MAP in conscious rats. Halothane (1.25%) almost completely inhibited these increases. 4. The results suggest that DPI causes a pressor response in conscious rats by activating the sympathetic nervous system and halothane abolishes this pressor response by inhibiting activities of the sympathetic nervous system. The results also show that influences of anaesthetics must be taken into consideration when evaluating pressor response of vasoactive agents.

Anesthetics↗
PubMed1993

Inhibitory actions of diphenyleneiodonium on endothelium-dependent vasodilatations in vitro and in vivo.

1. This study examined the in vitro and in vivo inhibitory effects of diphenyleneiodonium (DPI), a novel inhibitor of nitric oxide (NO) synthase, on endothelium-dependent vasodilatations. 2. DPI (3 x 10(-8)-3 x 10(-6) M) concentration-dependently inhibited acetylcholine (ACh)-induced relaxation in preconstricted rat thoracic aortic rings, with an IC50 of 1.8 x 10(-7) M and a maximal inhibition of nearly 100%. DPI (3 x 10(-6) M) also completely inhibited the relaxation induced by the calcium ionophore, A23187 but not by sodium nitroprusside (SNP). The inhibitory effect of DPI (3 x 10(-7) M) on ACh-induced relaxation was prevented by pretreatment with NADPH (5 x 10(-3) M) and FAD (5 x 10(-4) M) but not L-arginine (L-Arg, 2 x 10(-3) M). Pretreatment with NADPH did not alter the inhibitory effect of NG-nitro-L-arginine on ACh-induced relaxation. 3. The inhibitory effect of DPI on ACh-induced relaxation in the aortae lasted > 4 h after washout. In contrast to pretreatment, post-treatment (1 h later) with NADPH (5 x 10(-3) M) reversed only slightly the inhibitory effect of DPI. 4. In conscious rats, DPI (10(-5) mol kg-1) inhibited the depressor response to i.v. infused ACh, but not SNP. However, it caused only a transient pressor response which was previously shown to be due completely to sympathetic activation. 5. Thus, DPI is an efficacious and 'irreversible' inhibitor of endothelium-dependent vasodilatation in vivo and in vitro. The mechanism of the inhibition may involve antagonism of the effects of FAD and NADPH, co-factors of NO synthase. However, unlike the N0-substituted arginine analogues (another class of NO synthase inhibitors), DPI-induced suppression of endothelium-dependent vasodilatation in vivo does not lead to a sustained rise in blood pressure.

Acetylcholine↗
PubMed1985

The potential dependence of the intestinal Na+-dependent sugar transporter.

The unidirectional influx of the lipophilic cation tetraphenylphosphonium (TPP+) into isolated intestinal epithelial cells exhibits a marked dependence on the membrane potential (delta psi) maintained by or experimentally imposed on these cells. By taking advantage of this fact, we have described a "crossover" procedure that allows the relative permeability of a cation and anion pair to be determined. Measurements of such relative permeabilities permits diffusion potentials of defined magnitude to be imposed across the plasma membrane of ATP-depleted cells. This in turn allows description of the relationship between [14C]TPP+ influx and delta psi. We have determined that the flux-potential relationship is that predicted by the Goldman flux equation. Using this relationship as a calibration tool for delta psi, we then determined the quantitative relationship between membrane potential and the Na+-dependent influx of an actively transported sugar, alpha-methylglucoside (alpha-MG). The influx of [14C]alpha-MG also shows an exponential dependence on delta psi although it is more sharply potential dependent than that shown by TPP+. The specific relationship is consistent with that expected for a system with 2:1 Na+ stoichiometry which obeys the potential dependence predicted by Eyring rate theory with a single energy barrier occurring near the midpoint of the membrane. Over the range of potentials from +33 to -61 mV, we find no evidence for a minimum or threshold potential necessary to support transport and no evidence for an optimal potential that can maximize sugar transport. The data raise the possibility for using either [14C]TPP+ or [14C]alpha-MG influx as the basis for a new noninvasive procedure for measurement of delta psi.

Animals↗
PubMed1980

Properties of toxin-resistant sodium channels produced by chemical modification in frog skeletal muscle.

1. Single skeletal muscle fibres from the frog Rana pipiens were treated with the carboxyl group modifying reagent trimethyloxonium ion (TMO) and voltage clamped by the method of Hille & Campbell (1976). 2. TMO treatment reduced current through sodium channels to 0.33 +/- 0.03 that before treatment, but only 45 +/- 3% of this remaining current was blocked by 1 microM-tetrodotoxin (TTX) and only 37 +/- 5% by 100 nM-saxitoxin (STX). 3. This toxin resistance persisted in 90 microM-TTX, was not due to inactivation of toxin nor to components of the reaction solution other than TMO, but was prevented by the presence of 100 nM-STX during treatment with TMO. TMO-modified sodium channels can be blocked by the local anaesthetic lidocaine. 4. The permeabilities of TMO-modified channels to hydroxylammonium, ammonium, guanidinium, aminoguanidinium, methylammonium and tetramethylammonium ions relative to sodium were not significantly different from the permeabilities of untreated sodium channels. 5. Hydrogen ions blocked TMO-modified sodium channels, but the apparent pKa for block at +38 mV of 5.07 was significantly less than the corresponding value of 5.32 in untreated sodium channels. 6. It is suggested that TMO produces toxin resistance by esterifying an ionized carboxyl group which is an essential part of the toxin binding site. Such esterification would electrostatically reduce the local cation concentration, thus reducing the apparent pKa of hydrogen ion block and the single-channel conductance (Sigworth & Spalding, 1980). 7. It is concluded that the sodium channel contains a second acid group, near but distinct from an acid group previously hypothesized to be part of the selectivity filter and hydrogen ion binding site (Hille, 1971, 1972, 1975a).

Animals↗
PubMed1982

Interactions between three slow potassium responses controlled by three distinct receptors in Aplysia neurones.

1. A voltage clamp study was made of the K(+) permeability increases produced in certain identifiable neurones of the cerebral ganglion of Aplysia by any one of three distinct agonists (carbachol, histamine and dopamine).2. The three K(+) responses involve three distinct receptors, as shown by the selective effects of reversible antagonists (Gruol & Weinreich, 1979a) as well as by the differential, irreversible effects of trimethyloxonium (TMO) ions.3. Prolonged exposure of the neurones to one of the agonists reduces the response to the same agonist (desensitization) and, over the low concentration range, doubling the concentration of an agonist leads to supra-linear summation (potentiation).4. Prolonged exposure of the neurones to one of the agonists also reduces the response to the other agonists (cross-desensitization) and combined application of two agonists reveals cross-potentiation.5. The time course of desensitization (onset and decay) was the same for the histamine and carbachol responses and, except at very high concentration, was indistinguishable from that of cross-desensitization. Likewise, potentiation was similar in the two agonist systems and did not differ significantly from cross-potentiation.6. The results can be interpreted by assuming that the responses to the three agonists involve specific steps followed by common reaction steps, and that some of the common reaction steps control both potentiation and desensitization.7. The responses to carbachol and histamine differ in their voltage sensitivity. This suggests that one or more of the specific steps are voltage-sensitive.8. Although an increase of the intracellular Ca(2+) concentration can itself open K(+) channels, and also inhibit the responses to the three agonists, an increase of internal Ca(2+) does not appear to play an important role either in the development of the response or in the desensitization process.

Acetylcholine↗
PubMed1982

Stimulation of calcium-dependent release of labelled protein from pulse-labelled mouse pituitary intermediate lobe tissue.

1. The effect of K depolarization on the release of labelled protein from pulse-labelled intermediate lobe tissue of mouse pituitaries has been studied.2. Depolarization briefly stimulated Ca-dependent release of labelled protein. Co (2.5 mM) and verapamil (0.08 mM) reversibly blocked stimulation. Efflux of (45)Ca was also briefly stimulated by depolarization, but not in the presence of Co or verapamil, nor in the absence of Ca.3. The response to maintained depolarization quickly inactivated. Inactivation probably resulted from Ca-channel inactivation rather than exhaustion of available labelled protein, since responses different in magnitude but of constant time course could be obtained by depolarization in different concentrations of Ca. In addition, much more labelled protein could be released by exposure to Ba.4. Depolarization did not cause a response if the Ca concentration was 0.4 mM or less; neither did inactivation occur in these conditions, and a response occurred as soon as the Ca concentration was raised. Two separate responses could be generated by a stepwise increase in the Ca concentration during maintained depolarization. The magnitude of the two responses together was similar to the magnitude of one response at the higher Ca concentration.5. Recovery from inactivation was complete after about 20 min in normal K. However, recovery also occurred during maintained depolarization provided the Ca concentration was reduced sufficiently. Recovery was complete at 0.4 mM-Ca or less, and at higher concentrations the extent of recovery depended on the Ca concentration selected.6. It is concluded that depolarization opened potential-dependent Ca channels permitting Ca entry and causing the release of labelled products. The response was brief probably because the Ca channels were inactivated. Since the channels were not inactivated by depolarization in low Ca, inactivation may result from Ca entry.

Animals↗
PubMed2002

RopGAP4-dependent Rop GTPase rheostat control of Arabidopsis oxygen deprivation tolerance.

Transient soil flooding limits cellular oxygen to roots and reduces crop yield. Plant response to oxygen deprivation involves increased expression of the alcohol dehydrogenase gene (ADH) and ethanolic fermentation. Disruption of the Arabidopsis gene that encodes Rop (RHO-like small G protein of plants) guanosine triphosphatase (GTPase) activating protein 4 (ROPGAP4), a Rop deactivator, elevates ADH expression in response to oxygen deprivation but decreases tolerance to stress. Rop-dependent production of hydrogen peroxide via a diphenylene iodonium chloride-sensitive calcium-dependent reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is necessary for induction of both ADH and RopGAP4 expression. Tolerance to oxygen deprivation requires Rop activation and RopGAP4-dependent negative feedback regulation. This Rop signal transduction rheostat balances the ability to increase ethanolic fermentation with survival.

Alcohol Dehydrogenase↗
PubMed2005

A phenylalanine clamp catalyzes protein translocation through the anthrax toxin pore.

The protective antigen component of anthrax toxin forms a homoheptameric pore in the endosomal membrane, creating a narrow passageway for the enzymatic components of the toxin to enter the cytosol. We found that, during conversion of the heptameric precursor to the pore, the seven phenylalanine-427 residues converged within the lumen, generating a radially symmetric heptad of solvent-exposed aromatic rings. This "phi-clamp" structure was required for protein translocation and comprised the major conductance-blocking site for hydrophobic drugs and model cations. We conclude that the phi clamp serves a chaperone-like function, interacting with hydrophobic sequences presented by the protein substrate as it unfolds during translocation.

Amino Acid Sequence↗