PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “TMB”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

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

At least 19 recordsLinked to original sources
PubMed1990

TMB-8 as a pharmacologic tool in guinea pig myocardial tissues. I. Effects of TMB-8 on force of contraction and on action potential parameters in atrial and papillary muscles.

The compound 8-)N,N-diethylamino)-octyl-3,4,5-trimethoxybenzoate hydrochloride (TMB-8) had been introduced as an intracellular Ca++ antagonist. We have studied the effects of TMB-8 on electrical and mechanical activity of isolated cardiac tissues in order to estimate its spectrum of action in heart muscle. In spontaneously beating right atria of the guinea pig, TMB-8 (1-100 microM) had a negative chronotropic effect. In left atria, TMB-8 (1-100 microM) induced a frequency-dependent biphasic inotropic effect: A transient increase in force of contraction was followed by a sustained decrease; the latter could be antagonized partially by an increase in [Ca++]o. TMB-8 prolonged the time-to-peak force. At high concentrations of TMB-8 (greater than 10 microM), the electrical stimulation threshold was elevated. TMB-8 (20 microM) competitively inhibited the positive inotropic effect of Bay K 8644 and reduced the magnitude of the positive inotropic and/or chronotropic effects of veratridine, (-)-isoproterenol, forskolin, histamine and (-)-phenylephrine. TMB-8 (30 microM) prolonged the action potential duration (APD) [in particular at 90% of repolarization (APD90)] and the refractory period, and decreased the AP amplitude and Vmax. In right ventricular papillary muscles, TMB-8 (30 microM) shortened the APD (APD20 = APD50 greater than APD90) and the refractory period but hardly affected the AP amplitude and Vmax. The resting membrane potential remained unchanged in both tissues. These findings suggest that in addition to interference with the Ca++ release from the sarcoplasmic reticulum, TMB-8 also affects the membrane conductances for cations.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1990

TMB-8 as a pharmacologic tool in guinea pig myocardial tissues. II. Effects of TMB-8 on membrane currents in isolated ventricular cardiomyocytes.

In single isolated guinea pig ventricular cardiomyocytes, 8-(N,N-diethylamino)-octyl-3, 4, 5-trimethoxybenzoate hydrochloride (TMB-8) nonselectively inhibited membrane currents. TMB-8 concentration dependently and reversibly reduced calcium current (ICa) (pD2 5.0). The Ca++ channel blockade was only slightly use dependent. The steady-state inactivation curve of ICa was shifted to more negative membrane potentials by TMB-8; the curve for the normalized conductance of ICa was not significantly affected. The quasi steady-state K+ currents as a measure for K+ conductance were examined by means of slow depolarizing ramp pulses between -120 and +60 mV. In this potential range. TMB-8 (100 microM) reduced quasi steady-state potassium currents. The sodium current sodium current (INa) was investigated at low extracellular Na+ concentration (30 mM) after blocking ICa by Cd++ and reducing K+ currents (Cs+ substituted for K+). Under these conditions, TMB-8 concentration dependently and reversibly decreased INa (pD2 5.3), slightly shifted the steady-state inactivation curve of INa to more negative potentials and shifted the curve for the normalized conductance of INa to more positive potentials. We conclude that TMB-8 possesses both Ca++ channel- and Na+ channel-blocking properties and reduces the membrane K+ conductance. It is speculated that, because of its amphiphilic nature, TMB-8 accumulates at lipid-water interphase of biologic membranes and therefore interferes with the normal function of many membrane proteins.

Animals↗
PubMed1991

Inhibitory effect of 8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate (TMB-8) in vascular smooth muscle.

The inhibitory effects of 8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate (TMB-8) on vascular smooth muscle contraction and cytosolic Ca2+ level ([Ca2+]i) were examined using isolated rabbit aorta loaded with a fluorescent Ca2+ indicator, fura-2. TMB-8 (100 microM) decreased the high K(+)-induced increase in muscle tension, and [Ca2+]i and 45Ca2+ influx to their respective resting levels. TMB-8 (100 microM) almost completely inhibited the increase in [Ca2+]i and 45Ca2+ influx due to norepinephrine although muscle tension was only partially decreased. A higher concentration of TMB-8 (300 microM) inhibited the remaining portion of the contraction without additional decrease in [Ca2+]i. The inhibitory effect of TMB-8 on high K(+)-induced contraction, but not on the norepinephrine-induced contraction, was antagonized by the increase in external Ca2+ concentrations or by the Ca2+ channel activators, CGP 28,392 and by Bay K8644. In Ca(2+)-free solution, norepinephrine-induced transient increases in [Ca2+]i and muscle tension and 100 microM TMB-8 inhibited these changes. The caffeine-induced transient increases in [Ca2+]i and muscle tension were also inhibited by TMB-8 at concentrations higher than those needed to inhibit the norepinephrine-induced transient changes. In permeabilized smooth muscle, TMB-8 (300 microM) did not inhibit the Ca(2+)-induced contraction. These results suggest that TMB-8 inhibits vascular smooth muscle contractility by inhibiting Ca2+ influx, Ca2+ release and Ca2+ sensitization of contractile elements.

Animals↗
PubMed1992

Calcium-independent effects of TMB-8. Modification of phospholipid metabolism in neuroblastoma cells by inhibition of choline uptake.

TMB-8 [8-(NN-diethylamino)-octyl-3,4,5-trimethoxybenzoate] blocks agonist-stimulated release of Ca2+ from intracellular sites in many cell lines and is often used to distinguish between dependence on extracellular and intracellular Ca2+. In N1E-115 neuroblastoma cells, TMB-8 did not alter the resting cytosolic Ca2+ concentration in unstimulated cells, yet phospholipid metabolism was greatly affected. At concentrations of TMB-8 (25-150 microM) that inhibit Ca2+ release, phosphatidylcholine formation was inhibited, whereas synthesis of phosphatidylinositol, phosphatidylglycerol and phosphatidylserine was stimulated. Unlike other cationic amphipathic compounds, TMB-8 did not inhibit phosphatidate phosphatase or enzymes in the pathway from choline to phosphatidylcholine. Choline transport was the major site of action. TMB-8 was a competitive inhibitor (Ki = 10 microM) of low-affinity (Kt = 20 microM) choline transport. When added at the same time as labelled precursor, TMB-8 also decreased cellular uptake of phosphate and inositol, but not that of ethanolamine or serine. In prelabelled cells, continued uptake and incorporation of phosphate and inositol were not affected. Under these conditions phosphatidylinositol synthesis was increased 2-fold and, like the effect on phosphatidylcholine, reached a plateau at 100 microM-TMB-8. Phosphatidylglycerol synthesis increased linearly with TMB-8 concentration to 40-fold stimulation at 150 microM, suggesting a selective effect on synthesis of phosphatidylglycerol from CDP-diacylglycerol. Phosphatidylserine synthesis was also increased up to 3-fold. These Ca(2+)-independent effects limit the use of TMB-8 in studies of cell signalling that involve stimulated phosphatidylinositol and phosphatidylcholine metabolism.

Animals↗
PubMed1992

Electron microscopical demonstration of horseradish peroxidase by use of tetramethylbenzidine as chromogen and sodium tungstate as stabilizer (TMB-ST method): a tracing method with high sensitivity and well preserved ultrastructural tissue.

Until now methods using tetramethylbenzidine (TMB) for electron microscopy (TMB-EM methods) are all unable to provide a maximum demonstration of transported horseradish peroxidase (HRP) while maintaining good ultrastructural tissue preservation. In order to solve this problem, we have attempted to adapt a newly developed, highly sensitive TMB method using sodium tungstate (ST) as the stabilizer (TMB-ST method) for HRP electron microscopic retrograde and anterograde fiber tracing. The present study shows that the TMB-ST method combined with diaminobenzidine-cobalt (DAB-Co) is more sensitive than existing TMB-EM methods and that ultrastructural details are well preserved with this combined method. The resultant reaction product complex after osmication is stable and is observed as characteristic crystal-like structures which are extremely electron dense and often aggregated into clumps. In contrast, the TMB-ST method without the DAB-Co step frequently produces a moderate electron-dense reaction product. Therefore, we recommend the TMB-ST method combined with DAB-Co for HRP electron microscopy.

3,3'-Diaminobenzidine↗
PubMed1991

Calcium-dependent inhibition of renin secretion: TMB-8 is a non-specific antagonist.

Intracellular Ca (Cai) is an inhibitory second messenger in renin secretion, and it has been hypothesized that some first messengers--especially angiotensin II [A-II] and antidiuretic hormone [ADH], and possibly A1-adenosine receptor antagonists as well--increase Cai and thereby inhibit renin secretion by causing the release or mobilization of Ca from intracellular sites of sequestration. The present experiments were designed to test this hypothesis, by using 3,4,5-trimethoxybenzoic acid 8-(diethylamino)-octyl ester (TMB-8), a putative antagonist of Ca release from intracellular sequestration sites. The rat renal cortical slices preparation was used. Basal renin secretory rate was unaffected by 1 and 10 microM TMB-8, but more than doubled in response to 100 microM TMB-8. Basal renin secretory rate was inhibited by A-II (1 microM), by ADH (200 units/1), by an A1-adenosine receptor agonist (N6-cyclohexyladenosine, or CHA; 0.5 microM), and by an alpha-adrenergic agonist (methoxamine; 10 microM). Only the inhibitory effect of methoxamine was blocked by 1 and 10 microM TMB-8, but these concentrations had no effect on basal secretory rate. At 100 microM, TMB-8 blocked the inhibitory effects of ADH as well as of methoxamine, but failed to block the inhibitory effects of CHA and A-II. However, these observations cannot be taken as evidence that methoxamine and ADH, but not CHA and A-II, inhibit renin secretion by a mechanism involving release of Ca from intracellular sequestration sites, because 100 microM TMB-8 clearly had non-specific effects. Among them, it completely blocked the inhibitory effect of K-depolarization on renin secretion. Collectively, at least three separate actions of TMB-8 must be invoked to explain the present results. Likely candidates are an Na-channel blocking effect and a Ca channel blocking effect in addition to antagonism of the release of Cai.

Adenosine↗
PubMed1991

TMB-8 prevents the hydroosmotic response to ADH in rabbit cortical collecting tubules.

Both AVP and dDAVP effect a transient increase in cytosolic free calcium (iCa2+) in cortical collecting tubule (CCT) cells. To investigate the physiological role of this increase in iCa2+, we examined the effect of TMB-8, a putative inhibitor of iCa2+ release, on the initial and sustained phase of AVP- and dDAVP-stimulated water permeability (Pf) in isolated, perfused CCTs. Pretreatment of tubules with TMB-8, 50 microM, suppressed the increase in osmotic water permeability (Pf) induced by 10 microU/ml AVP and dDAVP, but had no effect on the sustained phase of the response. When increased to 100 microM. TMB-8 inhibited the sustained phase of AVP action. A similar pattern was observed on AVP-stimulated adenyly cyclase activity in rabbit renal membranes. Pretreatment of tubules with 50 microM TMB-8 attenuated the initial increase in Pf in response to cholera toxin but not to 8-Br-cAMP or forskolin. There was no effect of this concentration of TMB-8 on the sustained phase of these agonists. These studies suggest that, in lower concentrations, TMB-8 inhibits the mobilization of iCa2+, which is important for the interaction of Gs with the catalytic unit of adenylyl cyclase and the initial increase in AVP-stimulated Pf. In higher concentrations, TMB-8 inhibits adenylyl cyclase activity directly.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMedDate not supplied

Influence of 8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate (TMB-8) on cell cycle progression and proliferation of cultured arterial smooth muscle cells.

8-(N,N-Diethylamino)octyl-3,4,5-trimethoxybenzoate (TMB-8), a putative inhibitor of intracellular calcium mobilization, causes a dose-dependent inhibition of serum-induced proliferation of arterial smooth muscle cells in culture. Neither early rise in cytosolic calcium concentration nor induction of early induced cell cycle dependent genes (c-fos, ornithine decarboxylase) are inhibited after serum stimulation in presence of 100 microM TMB-8. In contrast, expression of thymidine kinase, a gene normally induced in late-G1 phase, is entirely inhibited by TMB-8. Taken together with flow cytometry studies, these results indicate that TMB-8 blocks cell cycle progression in mid- or late-G1 phase by a mechanism not directly related to early responses to serum stimulation since TMB-8 is also effective when introduced several hours after serum stimulation.

Animals↗
PubMed1990

Effects of a novel Ca2+ entry blocker, CD-349, and TMB-8 on renal vasoconstriction induced by angiotensin II and vasopressin in dogs.

The effects of a Ca2+ entry blocker CD-349 and an intracellular Ca2+ release inhibitor TMB-8 on renal vasoconstriction induced by angiotensin II (ANG II) and arg-vasopressin (AVP) were examined in anesthetized dogs. Intrarenal bolus injection of ANG II (3-10 ng/kg), AVP (5-20 ng/kg) or a Ca2+ entry promotor Bay K 8644 (0.1-0.4 micrograms/kg) produced a dose-dependent decrease in renal blood flow (RBF). Intrarenal infusion of CD-349 (0.03-0.3 micrograms/kg/min) suppressed the RBF responses to ANG II, AVP, and Bay K 8644. The RBF responses to ANG II and AVP were augmented slightly by intrarenal infusion of Bay K 8644 (0.3 micrograms/kg/min). Intrarenal infusion of TMB-8 (0.03-0.1 mg/kg/min) also suppressed the RBF responses to ANG II and AVP, whereas it did not affect the RBF response to Bay K 8644. These results suggest that vasoconstriction induced by ANG II or AVP is mediated both by the influx of Ca2+ through dihydropyridine-sensitive Ca2+ channels and the release of Ca2+ from TMB-8-sensitive Ca2+ pools in the in vivo dog kidney.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1991

Unspecific inhibition by the calmodulin antagonist calmidazolium and the intracellular calcium antagonist TMB-8 of the actions of sympathetic hepatic nerves and noradrenaline on glucose balance and flow in perfused rat liver.

In perfused rat liver hepatic nerve stimulation (10 Hz, 2 ms) (NS) increased glucose and lactate output, decreased flow and was accompanied by an overflow of noradrenaline into the hepatic vein. These effects were dependent on extracellular and partly on intracellular calcium. Infusion of noradrenaline (1 microM) (NA) elicited similar effects. 1) Calmidazolium at 1, 2 and 5 microM caused an increase in basal glucose output and a decrease and intrahepatic redistribution of flow after a lag of 30, 20 and 5 min, respectively. 2) After 5 min of 1 microM calmidazolium, i.e. before it altered basal metabolism and flow, the actions of NS and NA remained unaltered. 3) After 40 min of 1 microM calmidazolium, i.e. after it had just begun to alter basal metabolism and flow, NS caused a decrease in glucose and lactate output rather than an increase and the metabolic effects of NA were strongly reduced whereas the hemodynamic changes of both stimuli were not altered. 4) TMB-8 at 25, 50 and 100 microM caused a transient increase in lactate output and a decrease and intrahepatic redistribution of flow after a lag of 5 min only at 100 microM concentrations. 5) The effects of NS were inhibited already by 25 microM TMB-8 which reduced NA release whereas the effects of NA were not influenced. Thus, calmidazolium and TMB-8 did not act as a calmodulin and intracellular calcium antagonist, respectively, but had unspecific "side effects" in the complex system of the perfused liver. The antagonists cannot be used to study the role of intracellular calcium in intact organs.

Animals↗
PubMedDate not supplied

[Heightened anticholinesterase activity of chlorophos in its interaction with the TMB-4 reactivator in vitro].

Experiments in vitro demonstrated that a thermostatic treatment of an aqueous chlorophos solution at 38 degrees is attended by its increased cholinesterase activity. The speed of the process is much higher in an alkaline medium. A joint incubation of chlorophos with the TMB-4 reactivator of pH of 7.5 and 38 degrees not only fails to result in decomposition of the poison, but on the contrary, tends to speed up the progressive accretion of the inhibitory properties of this organophosphorus compound. The author considers the data obtained as one of the proofs pointing to the formation during direct interaction of TMB-4 with chlorophos or the product of its transformation of a stable complex appearing to be a powerful anticholinesterase agent.

Cholinesterase Inhibitors↗
PubMed1990

Influence of TMB-8 and calmidazolium on phorbol ester promoted histamine release from isolated rat mast cells.

The effects of TMB-8 and calmidazolium were investigated on mast cell responses believed to be mediated by protein kinase C, i.e. histamine release induced by TPA (tetradecanoyl-phorbol-acetate) in combination with sub-threshold concentrations of the ionophore A23187 and with antigen. Inhibition with both drugs was found in the same concentration range as observed earlier and could be counteracted by glucose, indicating an impaired oxidative energy production. Hence, the test drugs do not reveal protein kinase C selectivity.

Animals↗
PubMed1976

[Proposal of a new procedure for the exploration of hepatocellular function. The trimethoxybenzene test (TMB)].

The authors propose a new method of exploration of liver cell function based on the study of demethylation of a rapidly assimilated atoxic compound, trimethoxybenzene (TMB) in dimethoxy-hydroxybenzene (DMHB). Whereas in normal subjects, the urinary excretion of the metabolites was rapid and marked, 180 mg within 3 hours after taking a 400 mg dose, in patients with liver cell failure, the excretion of DMHB was considerably reduced, 80 to 95% in cirrhosis.

Benzene Derivatives↗
PubMed1979

[Changes in the transverse striated musculature during treatment with the pesticide, Neguvon, and TMB-4 reactivator].

The authors found that the contractile activity of isolated myofibers as-well as superprecipitation of myosin B were reduced after intoxication of white rats with 1/2 of dose of LD50 of neguvon. The reaktivator of cholinesterase TMB-4 (20 mg/kg) recovered the contractile capability of myofibres even on the third day after treatment, but superprecipitation of myosin B-after the twentieth day.

Animals↗
PubMed1976

[Antidotal effect of TMB-4 compos. Spofa in sheep intoxicated with O-ethyl S-(2-dimethylaminoethyl) methyl phosphonothioate].

A single application of a mixture of cholinolytic and reactivator of cholinesterase (TMB-4 compos. SPOFA) administered intravenously in the dose of 10.0 mg of trimedoxim per kg of live weight to sheep for 60 minutes after an intramuscular intoxication with O-ethyl S-(2-dimethylaminoethyl) methyl phosphonothioate (EDMM) in the dose of 0.00835 mg per kg of live weight (i.m. LD50, 2h) produces an immediate clinical effect. The reactivation of the erythrocytary acetyl cholinesterase (AChE, E.C.3.1.1.7.) examined in 15 minutes after the administration of the antidotal mixture is almost 100 p.c., the reactivation of the plasmatic butyryl cholin esterase (ChE, E.C.3.1.1.8.) approx. from 70 to 80 p. c. Restitution ad integrum occurred not later than in 14 days after the intoxication.

Animals↗