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At least 91 records · Page 5Linked to original sources
PubMed1989

Stimulative effects of TMB-8 and trifluoperazine on pancreatic hormone release.

The effects of 8-N-N-diethylamino octyl 3,4,5-trimethoxybenzoate (TMB-8) and trifluoperazine (TFP) on the early phase (10 min) of the release of pancreatic hormones from isolated rat islets were investigated. TMB-8 and TFP stimulated insulin, glucagon, and somatostatin release in a dose-dependent manner at a low glucose concentration (2.5 mM). The levels of glucagon and somatostatin release were also stimulated by these two agents at a high glucose concentration (10 mM). Their effects were independent of external calcium ion level. These two agents did not modify insulin release at the high glucose concentration. The stimulative effects of the two agents on the release of these hormones were partially suppressed when the islets were pretreated with 6-hydroxydopamine (6-OHDA), a chemical adrenergic denervator that acts at nerve endings. In this situation, the norepinephrine (NE) released from pancreatic islets decreased to 44% of that of non-treated islets (P less than 0.01). The addition of NE (10(-9) M) to the incubation medium increased insulin, glucagon, and somatostatin secretion by 20-30% over control levels (P less than 0.05). In conclusion, the early phase of pancreatic hormone release was stimulated by TMB-8 and TFP. Our results strongly suggest that these two drugs could be mediated by the NE released from nerve endings in the islets.

Animals↗
PubMed1980

Stabilizing and rapid thionin staining of TMB-based HRP reaction product.

Tetramethyl benzidine (TMB) as a substrate for horseradish peroxidase (HRP) histochemistry offers a great advantage over other substrates in its sensitivity but the reaction product is unstable in alcohol. Immersing TMB-reacted sections in methyl salicylate renders the reaction product stable enough so that exposure to ethanol for 10 min causes no detectable loss of HRP labelled neurons. A rapid thionin stain is introduced which, after stabilizing the TMB-based reaction product in methyl salicylate, causes no detectable loss of HRP labelled neurons. These procedures should prove valuable to users of the popular HRP techniques for studying neural connections.

Benzidines↗
PubMed1997

Behavioral comparison of the oximes TMB-4, 2-PAM, and HI-6 in rats using operant conditioning.

It has recently been shown that oximes can amplify the ability of cholinesterases to scavenge organophosphorus (OP) agents. Since both OP agents and oximes can disrupt performance, behavioral evaluation of bioscavenger therapies using oximes can be hindered. Therefore, we investigated the ability of three oximes, administered alone, to disrupt performance. The effects of trimedoxime bromide (TMB-4) (3.16-56.2 mg/kg), pralidoxime chloride (2-PAM) (10.0-237.1 mg/kg), and, 1-([[4-amincarbonyl)pyridino]-methoxy]-methyl)-2, 4-bis[(hydroxyimino)methyl] pyridinium dichloride monohydrate (HI-6) (10.0-237.1 mg/kg) were evaluated in rats using a variable-interval 56 (VI 56) s schedule of food reinforcement. Under control conditions, the VI 56 s schedule produced a constant rate of responding (i.e., lever-pressing). All three oximes produced dose-dependent decreases in responding, and the largest doses of TMB-4 and 2-PAM produced complete or nearly complete suppression of responding in all rats. Only the largest dose of HI-6 suppressed responding. Analysis of the dose-effect functions demonstrated that TMB-4 was substantially more potent than 2-PAM, which was slightly more potent than HI-6, for producing response suppression. These results establish doses of each oxime that will not contribute to disruption of responding, and thus, facilitate future evaluation of bioscavenger therapies against OP toxicity.

Animals↗
PubMed2004

Nimodipine and TMB-8 potentiate the AMPA-induced lesion in the basal ganglia.

Acute injection of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) into the rat globus pallidus leads to calcium precipitation, neuronal death and gliosis. In order to determine whether L-type calcium channels and/or release of Ca(2+) from intracellular stores contribute to the effects of AMPA, nimodipine and 8-(N,N-diethylamino) octyl-3,4,5-trimethoxybenzoate hydrochloride (TMB-8) were administered in combination with AMPA. Nimodipine, but not TMB-8, tended to exacerbate the calcification process initiated by AMPA; the AMPA/nimodipine/TMB-8 combination produced much more calcium deposition than AMPA (+62%, P<0.05). AMPA alone induced a slight but not significant astroglial reaction. Nimodipine slightly enhanced the astroglial reaction triggered by AMPA, whereas TMB-8 doubled it (P<0.001 versus AMPA). These data suggest that blockade of L-type calcium channels by nimodipine enhances calcium imbalance triggered by AMPA, and the calcium release from the endoplasmic reticulum does not participate in the AMPA-induced calcification.

Animals↗
PubMed1984

The intracellular calcium antagonist TMB-8 [8-(NN-diethylamino)octyl-3,4,5-trimethoxybenzoate] inhibits mitochondrial ATP production in rat thymocytes.

TMB-8 inhibited respiration of rat thymocytes and rat liver mitochondria, probably by inhibition of NADH dehydrogenase. TMB-8 markedly decreased both the cellular ATP concentration and the mitochondrial membrane potential in situ in thymocytes. These effects occurred at, or well below, the concentrations used in other systems to investigate the role of intracellular calcium pools in signalling events. We conclude that caution should be exercised in the interpretation of the effects of TMB-8.

Adenosine Triphosphate↗
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↗
PubMedDate not supplied

Influence of TMB-8 and thapsigargin on vasoconstrictor responses in the pulmonary vascular bed of the cat.

The effects of 8-(diethylamino)octyl-3,4,5-trimethoxybenzoate hydrochloride (TMB-8), a protein kinase C (PKC) inhibitor, and thapsigargin, a CaATPase inhibitor, on pressor responses were studied in the pulmonary vascular bed of the intact-chest anesthetized cat. Under conditions of constant lobar blood flow in the cat, injections of the angiotensin peptides (ANG II), norepinephrine (NE), serotonin (5-HT), Bay K 8644, and the thromboxane A2 mimic U46619 into the lobar arterial perfusion circuit caused dose-related increases in lobar arterial pressure and responses were reproducible with respect to time. Intravenous infusion of TMB-8 at 1.0 mug . kg reduced the pressor response to the ANG II and to NE. However, TMB-8 did not alter pressor responses to 5-HT, U46619, or Bay K 8644. In a separate series of experiments, the effects of thapsigargin were investigated and intravenous infusion of the CaATPase inhibitor at 1.0 mug . kg also reduced pressor responses to the ANG II and to NE but did not alter pressor responses to 5-HT, U46619, and Bay K 8644. The data provide support for the hypothesis that vasoconstrictor responses to ANG II and NE in the pulmonary vascular bed are mediated in part by the activation of protein kinase C (PKC) and sarcoplasmic reticulum CaATPase-sensitive mechanisms in the cat. The present data suggest that pulmonary pressor responses to U46619, 5-HT, and Bay K 8644 are not mediated by PKC or CaATPase activation in the pulmonary vascular bed of the cat.

Animals↗
PubMed1991

Natriuretic effect of TMB-8 in anaesthetized dogs.

1. Effects of 8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate hydrochloride (TMB-8), an inhibitor of intracellular calcium release, on renal function were examined in anaesthetized dogs. 2. Intrarenal arterial infusion of TMB-8 (0.03 and 0.1 mg/kg per min) increased urine flow rate, urinary sodium excretion and fractional excretion of sodium without affecting blood pressure, renal blood flow or glomerular filtration rate. 3. The results suggest that TMB-8 inhibits tubular sodium reabsorption to induce natriuresis.

Animals↗
PubMed1984

Inhibition of antigen- and calcium ionophore A23187-induced contractions of guinea pig isolated airways with 8-(diethylamino)octyl-3,4,5-trimethoxybenzoate hydrochloride (TMB-8).

Both antigen- and calcium ionophore A23187-induced airways contractions are dependent on increased concentrations of intracellular calcium. Challenge of isolated tracheal spirals and parenchymal strips from sensitized guinea pigs with antigen or calcium ionophore A23187 in the presence of the intracellular calcium antagonist, 8-(diethylamino)octyl-3,4,5-trimethoxybenzoate hydrochloride (TMB-8), resulted in significantly reduced contractions. The results demonstrated that TMB-8 inhibits events that are dependent on either mobilization of intracellular calcium (i.e. antigen) or entry of calcium from extracellular sources (i.e. calcium ionophore A23187). The efficacy of TMB-8 in this model suggests that intracellular calcium antagonists may be potentially useful in the therapy of asthma.

Animals↗
PubMed1987

Inhibition of antigen-induced contraction of guinea pig isolated tracheal muscle with 2-n-butyl-3-dimethylamino-5,6-methylenedioxy indene (MDI-A), indane (MDI-B) and 8-(diethylamino)octyl-3,4,5-trimethoxy benzoate hydrochloride (TMB-8).

The effects of three intracellular calcium antagonists on antigen-induced contraction of sensitized guinea pig tracheal muscle were investigated. The agents employed were: 2-n-butyl-3-dimethylamino-5,6-methylenedioxy indene hydrochloride (MDI-A), 2-n-butyl-3-dimethylamino-5,6-methylenedioxy indane hydrochloride (MDI-B) and 8-(diethylamino)octyl-3,4,5-trimethoxy benzoate hydrochloride (TMB-8). Each of these agents caused a concentration-dependent inhibition of the antigen-induced contraction of sensitized tracheal smooth muscle. Moreover, in histamine and leukotriene D4 (LTD4) incited contractions of guinea pig tracheal muscle, they showed antagonistic action. The induced tracheal muscle contraction, achieved through the addition of compound 48/80 to a solution of ethylene glycol bis (beta-aminoethylether)-N,N,N1, N1-tetraacetic acid (EGTA) in a contained Ca-free medium, was completely inhibited by individual pretreatment with MDI-A, MDI-B and TMB-8. In the case of tracheal muscle contraction induced by CaCl2 in a high potassium, Ca-free medium, only TMB-8 inhibited contraction. Lastly, none of these three intracellular calcium antagonists affected the antigen-induced release of histamine and slow reacting substance of anaphylaxis (SRS-A). These results suggest that MDI-A and MDI-B inhibit the antigen-induced contraction of sensitized guinea pig tracheal muscle by interfering with the contractile responses caused by histamine and LTD4.

Animals↗
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

Metabolic disposition of the alkylphosphate antagonist, 1,1'-trimethylenebis(4-aldoximinopyridinium) ion (TMB-4), in the rat. III. Trimethylene-1-(4-aldoximinopyridinium)-1'-(4-carboxamidopyridinium) ion.

1,1'-Trimethylene [1,1'-14C]bis(4-aldoximinopyridinium) ion (TMB-4) was synthesized and its metabolic disposition was investigated in vivo. Rats were administered multiple doses of TMB-4 (25 mg/kg) by the intraperitoneal route and urine was collected over a 48-hr period. Approximately 98% of the administered radioactive dose could be accounted for in the urine during that time. A urinary metabolite, trimethylene-1-(4-aldoximinopyridinium)-1'-(4-carboxamidopyridinium) ion (TACARB), was isolated by ethanol extraction, charcoal adsorption chromatography, and ion-exchange chromatography. The metabolite was then characterized by comparing its spectral, chromatographic, and electrophoretic properties with those of authentic TACARB ion. Possible reaction mechanisms involved in the biochemical pathways for the formation of this metabolite from TMB-4 are discussed.

Animals↗
PubMed1989

The effects of TMB-8 on the shape changes of vascular endothelial cells resulting from exposure to various inflammatory agents.

Pre-treatment of the endothelial cells lining the guinea pig inferior vena cava with 8-(diethylamino)octyl 3,4,5-trimethoxybenzoate (TMB-8) (10 microM) in vitro significantly reduced the shape changes resulting from subsequent exposure to platelet activating factor (PAF) (0.1 microM), calcium ionophore A23187 (10 microM), histamine (300 microM), bradykinin (2 microM), prostaglandin E2 (PGE2) (30 microM), or leukotrienes (LT) C4, D4 or E4 (1 microM). Since TMB-8 is an intracellular calcium antagonist, this provides evidence to support the suggestion that these inflammatory agents increase the concentration of intracellular calcium which brings about a contraction of the actin-myosin complex resulting in endothelial cell shape changes, and the formation of interendothelial cell gaps.

Animals↗
PubMed1987

Effects of TMB-8, a calcium antagonist, on transport properties of the isolated canine tracheal epithelium.

The effects of the putative intracellular Ca2+ antagonist, TMB-8 (8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate), on the canine tracheal epithelium were examined. Luminal addition reduced rapidly, but reversibly, the transmucosal potential difference and increased the resistance across the open-circuited epithelium. Under short-circuit conditions, the drug reduced stimulation by prostaglandin E2, forskolin, 8-bromo cyclic AMP, prostaglandin F2 alpha and A23187. Inhibition of prostaglandin E2 responses were accompanied by reversal of net Cl- fluxes produced by the agonist. The effects of TMB-8 were unaffected by increasing Ca2+ in the bathing solutions, and were not mimicked by procaine, nitrendipine, calmidazolium, compound 48/80 or trifluoperazine. W7 did, to a limited extent, produce similar responses, though the drug was more toxic, and the effects were irreversible.

1-Methyl-3-isobutylxanthine↗
PubMed1987

Combined GABA-immunocytochemistry and TMB-HRP histochemistry of pretectal nuclei projecting to the inferior olive in rats, cats and monkeys.

Cells in the pretectal nucleus of the optic tract (NOT) of rats, cats and monkeys were retrogradely labeled with horseradish peroxidase (HRP) stereotaxically injected into the inferior olive (IO). A procedure for stabilizing the tetramethylbenzidine (TMB)-HRP reaction product was used to visualize combined TMB-HRP and immunohistochemically localized gamma-aminobutyric acid (GABA) in the same sections. Positive GABAergic reaction product was found to be restricted to smaller-size intrinsic neurons. Larger NOT cells projecting to the IO were consistently free of GABA reaction product and, in addition, appeared to be contacted by relatively few GABAergic terminals.

Animals↗
PubMed1993

Effects of nifedipine and TMB-8 on renal vasoconstriction induced by hypertonic saline in dogs.

Intrarenal arterial infusion of hypertonic saline (+30 mEq/l NaCl in renal plasma) reduced renal blood flow and glomerular filtration rate with little change in filtration fraction in anesthetized dogs. The blood flow and the filtration rate responses were suppressed during infusion of nifedipine (0.1 microgram/kg per min). TMB-8 (50 micrograms/kg per min) also suppressed the blood flow response but not the filtration rate response. These results suggest that preglomerular vasoconstriction during hypertonic saline infusion requires Ca2+ influx via voltage-dependent Ca2+ channels and that hypertonic saline slightly contracts postglomerular vessels by activating a TMB-8-sensitive Ca2+ movement pathway.

Animals↗
PubMed1993

Use of bimanyl actin derivative (TMB-actin) for studying complexation of beta-thymosins. Inhibition of actin polymerization by thymosin beta 9.

By reacting trimethylammoniobromobimane bromide (TMB bromide) with rabbit muscle actin, a fluorescent reporter group was linked to cysteine at position 374. Fluorescence of TMB-actin decreased significantly on addition of thymosin beta 4 (T beta 4), a peptide of 43 amino acid residues reported to bind to monomeric actin and to prevent filament formation. Based on this effect, we determined the KD value of the thymosin beta 4 complex as 0.8 microM, a value that is in agreement with previous determinations. In addition to the main compound thymosin beta 4, bovine tissue contains a related peptide, thymosin beta 9 (T beta 9), which has 41 amino acid residues and ca. 75% sequence homology. In the present study we show for the first time that T beta 9, similar to T beta 4, forms a 1:1 complex with monomeric actin, and hereby inhibits actin polymerization. With a KD value of 1.1 microM the affinity of T beta 9 is in the same range as that of T beta 4, suggesting that T beta 9, like T beta 4, contributes to maintaining the pool of monomeric actin in bovine non-muscle cells. Further proof of the interaction of T beta 9 with actin was provided by native PAGE, where the complex showed the reported higher mobility, as well as by crosslinking experiments. Using different crosslinking reagents, like water-soluble carbodiimide (EDC), m-maleimidobenzoyl-N-hydroxysuccinimidate (MBS), and disuccinimidylsuberate (DSS), we were able to produce conjugates of 47 kDa. In one of these (from MBS) both actin and T beta 9 could be identified by immunoblotting. When, in the MBS crosslinking experiments, native actin was replaced with (374-NEM)-actin, the 47 kDa band was not seen, indicating that Cys-374 takes part in the thiol-specific crosslinking reaction. This suggests that part of the binding site of T beta 9 must be located close to the carboxy-terminus.

Actins↗