“The flavor enhancer maltol increases pigment aggregation in dermal and neural melanophores in Xenopus laevis tadpoles”

ABSTRACTMelanophores are pigmented cells that change the distribution of pigmented melanosomes, enabling animals to appear lighter or darker for camouflage, thermoregulation, and UV-protection. A complex series of hormonal and neural mechanisms regulates melanophore pigment distribution, making these cells a valuable tool to screen toxicants as a dynamic cell type that responds rapidly to the environment. We found that maltol, a naturally occurring flavor enhancer and fragrance agent, induces melanophore pigment aggregation in a dose-dependent manner in Xenopus laevis tadpoles. To determine if maltol affects camouflage adaptation, we placed tadpoles into maltol baths situated over either white or black background. Maltol induced pigment aggregation in a similar dose-dependent pattern regardless of background color. We also tested how maltol treatment compares to melatonin treatment and found that the degree of pigment aggregation induced by maltol is similar to treatment with melatonin, but the time course differs significantly. Last, maltol had no effect on mRNA expression of pro-opiomelanocortin or melanin concentrating hormone receptor in the brain, both of which regulate camouflage-related pigment aggregation. Our results suggest that maltol does not exert its effects via the camouflage adaptation mechanism nor via melatonin-based mechanisms. These results are the first to identify a specific toxicological effect of maltol exposure and rules out several mechanisms by which maltol may exert its effects on pigment aggregation.

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Intracerebroventricular injection of prostaglandin E2 increases splenic sympathetic nerve activity in rats

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1995.269.3.r662 ◽

1995 ◽

Vol 269 (3) ◽

pp. R662-R668 ◽

Cited By ~ 5

Author(s):

T. Ando ◽

T. Ichijo ◽

T. Katafuchi ◽

T. Hori

Keyword(s):

Prostaglandin E2 ◽

Sympathetic Nerve ◽

Time Course ◽

Sympathetic Nerve Activity ◽

Dependent Manner ◽

Central Administration ◽

Nerve Activity ◽

High Doses ◽

Alpha Chloralose ◽

Dose Dependent

The effects of central administration of prostaglandin E2 (PGE2) and its selective agonists on splenic sympathetic nerve activity (SNA) were investigated in urethan- and alpha-chloralose-anesthetized rats. An intra-third-cerebroventricular (13V) injection of PGE2 (0.1-10 nmol/kg) increased splenic SNA in a dose-dependent manner. An I3V injection of an EP1 agonist, 17-phenyl-omega-trinor PGE2 (1-30 nmol/kg), also resulted in a dose-dependent increase in splenic SNA, with a time course similar to that of PGE2-induced responses. In contrast, EP2 agonists, butaprost (10-100 nmol/kg I3V) and 11-deoxy-PGE1 (10-100 nmol/kg I3V), had no effect on splenic SNA. An I3V injection of M & B-28767 (an EP3/EP1 agonist, EP3 >> EP1) increased splenic SNA only at high doses (10-100 nmol/kg). Pretreatment with an EP1 antagonist, SC-19220 (200 and 500 nmol/kg), completely blocked the responses of splenic SNA to PGE2 (0.1 nmol/kg) and M & B-28767 (10 nmol/kg), respectively. These findings indicate that brain PGE2 increases splenic SNA through its action on EP1 receptors.

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Phasic Genioglossus and Palatoglossus Muscle Activity during Recovery from Sevoflurane Anesthesia

Anesthesiology ◽

10.1097/aln.0b013e318295a27b ◽

2013 ◽

Vol 119 (3) ◽

pp. 562-568 ◽

Cited By ~ 2

Author(s):

Ilavajady Srinivasan ◽

Samuel Strantzas ◽

Mark W. Crawford

Keyword(s):

Muscle Activity ◽

Upper Airway ◽

Dependent Manner ◽

Sevoflurane Anesthesia ◽

Phasic Activity ◽

Similar Dose ◽

Inhalational Anesthetic ◽

Recovery From Anesthesia ◽

End Tidal ◽

Dose Dependent

Abstract Background: Inhalational anesthetic effects on upper airway muscle activity in children are largely unknown. The authors tested the hypothesis that phasic inspiratory genioglossus and palatoglossus activity increases during recovery from sevoflurane anesthesia in a dose-dependent manner in children. Methods: Sixteen children, aged 2.0 to 6.9 yr, scheduled for elective urological surgery were studied. Electromyogram recordings were acquired using intramuscular needle electrodes during spontaneous ventilation. After a 15-min period of equilibration, electromyogram activity was recorded over 30 s at each of three end-tidal concentrations, 1.5, 1.0, and 0.5 minimum alveolar concentration (MAC), administered in sequence. Results: Phasic genioglossus activity was noted in four children at 1.5 MAC, five at 1.0 MAC, and six children at 0.5 MAC sevoflurane. Phasic palatoglossus activity was noted in 4 children at 1.5 MAC, 6 at 1.0 MAC, and 10 children at 0.5 MAC sevoflurane. Both the proportion of children exhibiting phasic activity, and the magnitude of phasic activity increased during recovery from anesthesia. For the genioglossus, decreasing the depth of sevoflurane anesthesia from 1.5 to 1.0 MAC increased phasic activity by approximately 35% and a further decrease to 0.5 MAC more than doubled activity (median [range] at 1.5 and 0.5 MAC: 2.7 μV [0 to 4.0 μV] and 8.6 μV [3.2 to 17.6], respectively; P = 0.029). A similar dose-related increase was recorded at the palatoglossus (P = 0.0002). Conclusions: Genioglossus and palatoglossus activity increases during recovery from sevoflurane anesthesia in a dose-dependent manner over the clinical range of sevoflurane concentrations in children.

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Endogenous H2S is required for hypoxic sensing by carotid body glomus cells

AJP Cell Physiology ◽

10.1152/ajpcell.00100.2012 ◽

2012 ◽

Vol 303 (9) ◽

pp. C916-C923 ◽

Cited By ~ 48

Author(s):

Vladislav V. Makarenko ◽

Jayasri Nanduri ◽

Gayatri Raghuraman ◽

Aaron P. Fox ◽

Moataz M. Gadalla ◽

...

Keyword(s):

Carotid Body ◽

Time Course ◽

Channel Blocker ◽

Primary Site ◽

Dependent Manner ◽

Free Medium ◽

Adult Rats ◽

Glomus Cells ◽

Dose Dependent ◽

Carotid Body Glomus Cells

H2S generated by the enzyme cystathionine-γ-lyase (CSE) has been implicated in O2 sensing by the carotid body. The objectives of the present study were to determine whether glomus cells, the primary site of hypoxic sensing in the carotid body, generate H2S in an O2-sensitive manner and whether endogenous H2S is required for O2 sensing by glomus cells. Experiments were performed on glomus cells harvested from anesthetized adult rats as well as age and sex-matched CSE+/+ and CSE−/− mice. Physiological levels of hypoxia (Po2 ∼30 mmHg) increased H2S levels in glomus cells, and dl-propargylglycine (PAG), a CSE inhibitor, prevented this response in a dose-dependent manner. Catecholamine (CA) secretion from glomus cells was monitored by carbon-fiber amperometry. Hypoxia increased CA secretion from rat and mouse glomus cells, and this response was markedly attenuated by PAG and in cells from CSE−/− mice. CA secretion evoked by 40 mM KCl, however, was unaffected by PAG or CSE deletion. Exogenous application of a H2S donor (50 μM NaHS) increased cytosolic Ca2+ concentration ([Ca2+]i) in glomus cells, with a time course and magnitude that are similar to that produced by hypoxia. [Ca2+]i responses to NaHS and hypoxia were markedly attenuated in the presence of Ca2+-free medium or cadmium chloride, a pan voltage-gated Ca2+ channel blocker, or nifedipine, an L-type Ca2+ channel inhibitor, suggesting that both hypoxia and H2S share common Ca2+-activating mechanisms. These results demonstrate that H2S generated by CSE is a physiologic mediator of the glomus cell's response to hypoxia.

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Effects of pinacidil on coronary Ca2+-myosin phosphorylation in cold potassium cardioplegia model

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.2000.279.3.h882 ◽

2000 ◽

Vol 279 (3) ◽

pp. H882-H888 ◽

Cited By ~ 2

Author(s):

Naruto Matsuda ◽

Kathleen G. Morgan ◽

Frank W. Sellke

Keyword(s):

Time Course ◽

Dependent Manner ◽

Coronary Smooth Muscle ◽

Intracellular Ca ◽

No Signaling ◽

Synthase Inhibitor ◽

Mlc Phosphorylation ◽

Dose Dependent ◽

Cardioplegic Solutions

The effects of the potassium (K+) channel opener pinacidil (Pin) on the coronary smooth muscle Ca2+-myosin light chain (MLC) phosphorylation pathway under hypothermic K+cardioplegia were determined by use of an in vitro microvessel model. Rat coronary arterioles (100–260 μm in diameter) were subjected to 60 min of simulated hypothermic (20°C) K+cardioplegic solutions (K+= 25 mM). We first characterized the time course of changes in intracellular Ca2+concentration, MLC phosphorylation, and diameter and observed that the K+cardioplegia-related vasoconstriction was associated with an activation of the Ca2+-MLC phosphorylation pathway. Supplementation with Pin effectively suppressed the Ca2+accumulation and MLC phosphorylation in a dose-dependent manner and subsequently maintained a small decrease in vasomotor tone. The ATP-sensitive K+(KATP)-channel blocker glibenclamide, but not the nitric oxide (NO) synthase inhibitor Nω-nitro-l-arginine methyl ester, significantly inhibited the effect of Pin. K+cardioplegia augments the coronary Ca2+-MLC pathway and results in vasoconstriction. Pin effectively prevents the activation of this pathway and maintains adequate vasorelaxation during K+cardioplegia through a KATP-channel mechanism not coupled with the endothelium-derived NO signaling cascade.

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Effect of cocaine and methylecgonidine on intracellular Ca2+ and myocardial contraction in cardiac myocytes

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1997.273.2.h893 ◽

1997 ◽

Vol 273 (2) ◽

pp. H893-H901 ◽

Cited By ~ 1

Author(s):

L. Huang ◽

J. H. Woolf ◽

Y. Ishiguro ◽

J. P. Morgan

Keyword(s):

Structural Damage ◽

Time Course ◽

Crack Cocaine ◽

Pyrolysis Product ◽

Myocardial Contraction ◽

Dependent Manner ◽

Response Curves ◽

Inotropic Effects ◽

Cell Shortening ◽

Dose Dependent

We evaluated the cardiac effects of the principle pyrolysis product of crack cocaine smoking, methylecgonidine (MEG), in comparison with cocaine. Peak cell shortening and intracellular Ca2+, as detected by the Ca2+ indicator indo 1, were recorded in enzymatically isolated ferret myocytes. Both cocaine and MEG decreased peak cell shortening and peak intracellular Ca2+ concentration ([Ca2+]i) in a dose-dependent manner (10(-8)-10(-4) M). MEG shifted the peak [Ca2+]i-to-peak shortening relationship downward and was more potent than cocaine. Atropine (10(-6) M) upwardly shifted the dose-response curves of MEG, cocaine, and carbachol but not of procaine. The negative inotropic effects of MEG were inhibited by methoctramine, a selective M2 receptor blocker but not by M1 (pirenzepine) or M3 (4-diphenylacetoxy-N-methylpiperidine methiodide) blocking agents. In contrast to cocaine, the effects of large doses of MEG were irreversible over the time course of our experiments, raising the possibility of structural damage. We conclude that MEG acts primarily on M2 cholinergic receptors in the heart to produce acute cardiac intoxication and, in contrast to cocaine, may decrease the myofilament Ca2+ responseness and cause structural damage to myocytes by a direct toxic effect.

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PK11195 Effect on Steroidogenesis Is Not Mediated Through the Translocator Protein (TSPO)

Endocrinology ◽

10.1210/en.2014-1707 ◽

2015 ◽

Vol 156 (3) ◽

pp. 1033-1039 ◽

Cited By ~ 52

Author(s):

Lan N. Tu ◽

Amy H. Zhao ◽

Douglas M. Stocco ◽

Vimal Selvaraj

Keyword(s):

Translocator Protein ◽

Mitochondrial Outer Membrane ◽

Dependent Manner ◽

Tumor Cell Lines ◽

Dibutyryl Camp ◽

Progesterone Production ◽

Similar Dose ◽

Leydig Tumor Cells ◽

Steroidogenic Cells ◽

Dose Dependent

Abstract Translocator protein (TSPO) is a mitochondrial outer membrane protein of unknown function with high physiological expression in steroidogenic cells. Using TSPO gene–deleted mice, we recently demonstrated that TSPO function is not essential for steroidogenesis. The first link between TSPO and steroidogenesis was established in studies showing modest increases in progesterone production by adrenocortical and Leydig tumor cell lines after treatment with PK11195. To reconcile discrepancies between physiological and pharmacological interpretations of TSPO function, we generated TSPO-knockout MA-10 mouse Leydig tumor cells (MA-10:TspoΔ/Δ) and examined their steroidogenic potential after exposure to either dibutyryl-cAMP or PK11195. Progesterone production in MA-10:TspoΔ/Δ after dibutyryl-cAMP was not different from control MA-10:Tspo+/+ cells, confirming that TSPO function is not essential for steroidogenesis. Interestingly, when treated with increasing concentrations of PK11195, both control MA-10:Tspo+/+ cells and MA-10:TspoΔ/Δ cells responded in a similar dose-dependent manner showing increases in progesterone production. These results show that the pharmacological effect of PK11195 on steroidogenesis is not mediated through TSPO.

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Effect of retinoic acid on limb regeneration in Xenopus laevis

Canadian Journal of Zoology ◽

10.1139/z83-356 ◽

1983 ◽

Vol 61 (12) ◽

pp. 2698-2702 ◽

Cited By ~ 2

Author(s):

Steven R. Scadding

Keyword(s):

Retinoic Acid ◽

Xenopus Laevis ◽

Limb Regeneration ◽

Dependent Manner ◽

African Clawed Frog ◽

Long Term Effect ◽

Aquarium Water ◽

Dose Dependent ◽

Clawed Frog

The objective of this experiment was to determine the effect of retinoic acid on the process of limb regeneration in the African clawed frog, Xenopus laevis. Limbs were bilaterally amputated through the radio-ulna and then treated for 15 days with retinoic acid in the aquarium water, at 3, 15, or 75 IU/mL. The retinoic acid inhibited limb regeneration in a dose-dependent manner, reduced the length of the regenerates, and produced irregularities in the morphogenesis of the cartilage rod in the regenerate. The regenerated limbs were removed after 150 days by amputation through the humerus, and the limbs were again allowed to regenerate. In the retinoic acid treated animals, despite the fact that retinoic acid treatment had been discontinued over 4 months previously, limb regeneration was still inhibited. These results suggest that retinoic acid has a long-term effect on the treated animals.

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NH3 permeation through the apical membrane of MDCK cells is via a lipid pathway

AJP Renal Physiology ◽

10.1152/ajprenal.1988.255.1.f135 ◽

1988 ◽

Vol 255 (1) ◽

pp. F135-F141

Author(s):

K. Golchini ◽

I. Kurtz

Keyword(s):

Activation Energy ◽

Acetic Acid ◽

Plasma Membrane ◽

Time Course ◽

Apical Membrane ◽

Mdck Cells ◽

Disulfonic Acid ◽

Dependent Manner ◽

Cell Monolayers ◽

Dose Dependent

The pathway for NH3 permeation across the apical membrane of MDCK cells was determined by measuring the effect of membrane fluidizing agents, protein reactive agents, and temperature on cellular NH3 influx. The rate of NH3 influx was calculated from the time course of increase in intracellular pH (pHi), measured with 2,7-biscarboxyethyl-5(6)-carboxyfluorescein, when MDCK cell monolayers were exposed to NH4Cl. The apical membrane NH3 permeability was 7.13 +/- 0.37 x 10(-3) cm/s (n = 12) at 37 degrees C and 1.23 +/- 0.07 x 10(-3) cm/s (n = 7) at 18 degrees C. In comparison, apical membrane permeability at 37 degrees C to the weak acids, valeric acid and acetic acid, were 1.39 +/- 0.11 x 10(-2) cm/s (n = 4) and 6.93 +/- 0.11 x 10(-3) cm/s (n = 4), respectively. The activation energy for NH3 permeation was 15.0 +/- 1.0 kcal/mol (17.5 degrees C-37.5 degrees C). In the presence of the membrane fluidizing agents, heptanol or chloroform, NH3 permeability increased in a dose-dependent manner. Heptanol (15 mM) significantly decreased the activation energy for NH3 permeation to 4.4 +/- 0.6 kcal/mol, P less than 0.001. The carboxyl reactive agent (1-cyclohexyl-3-(2-morpholinoethyl)carbodiimide metho-p-toluensulfonic acid 1 mM), aminoreactive agents (4,4'-diisothiocyanostilbene-2,2'-disulfonic acid 50 microM; picrylsulphonic acid 1 mM), the sulphydryl reactive agent (p-chloromercuriphenylsulfonic acid 1 mM), and the nonspecific membrane protein cleaving agent pronase (1 mg/ml) had no effect on the NH3 influx. The results suggest that NH3 permeates the plasma membrane of MDCK cells via a lipid pathway.

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Differential pathways (phospholipase C and phospholipase D) of bradykinin-induced biphasic 1,2-diacylglycerol formation in non-transformed and K-ras-transformed NIH-3T3 fibroblasts. Involvement of intracellular Ca2+ oscillations in phosphatidylcholine breakdown

Biochemical Journal ◽

10.1042/bj2830347 ◽

1992 ◽

Vol 283 (2) ◽

pp. 347-354 ◽

Cited By ~ 36

Author(s):

T Fu ◽

Y Okano ◽

Y Nozawa

Keyword(s):

Phospholipase C ◽

Phospholipase D ◽

Dependent Manner ◽

3T3 Cells ◽

3T3 Fibroblasts ◽

Similar Dose ◽

A Cell ◽

Nih 3T3 ◽

Dose Dependent ◽

Nih 3T3 Cells

Bradykinin (BK) induced a biphasic increase in 1,2-diacylglycerol (DAG) in both K-ras-transformed fibroblasts (DT) and the parent NIH-3T3 cells. The first phase was coincident with the increase in Ins(1,4,5)P3 resulting from PtdIns(4,5)P2 hydrolysis, and the second, sustained, phase was derived from phosphatidylcholine (PtdCho) hydrolysis. In NIH-3T3 cells, stimulation by BK induced greater production of choline than phosphocholine in [3H]choline-labelled cells and appreciable phosphatidylethanol (PtdEtOH) formation in [3H]myristic acid-labelled cells, suggesting that PtdCho was hydrolysed mainly by a phospholipase D (PLD) activity. Pretreatment with propranolol, an inhibitor of phosphatidate phosphohydrolase, markedly diminished the second DAG accumulation, supporting the above notion. In DT cells, BK induced predominantly phosphocholine generation and little PtdEtOH formation, indicating that the PtdCho hydrolysis was due to a phospholipase C (PLC) activity. The BK-induced oscillations in intracellular Ca2+ concentration ([Ca2+]i) observed in single DT cells [Fu, Sugimoto, Oki, Murakami, Okano & Nozawa (1991) FEBS Lett. 281, 263-266] were detected as a sustained [Ca2+]i elevation when assayed in a cell suspension. A receptor-operated Ca2+ channel blocker, SK&F 96365, suppressed both the BK-induced phosphocholine generation and the sustained [Ca2+]i elevation in a similar dose-dependent manner. These results thus suggested that oscillations in [Ca2+]i are involved in the activation of PtdCho-specific PLC in DT cells.

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