Self-Inhibition in Ca2+-Evoked Taste Responses: A Novel Tool for Functional Dissection of Salt Taste Transduction Mechanisms

1998 ◽  
Vol 79 (2) ◽  
pp. 911-921 ◽  
Author(s):  
Mamoun A. Kloub ◽  
Gerard L. Heck ◽  
John A. Desimone

Kloub, Mamoun A., Gerard L. Heck, and John A. DeSimone. Self-inhibition in Ca2+-evoked taste receptors: a novel tool for functional dissection of salt taste transduction mechanisms. J. Neurophysiol. 79: 911–921, 1998. Rat chorda tympani (CT) responses to CaCl2 were obtained during simultaneous current and voltage clamping of the lingual receptive field. Unlike most other salts, CaCl2 induced negatively directed transepithelial potentials and gave CT responses that were auto-inhibitory beyond a critical concentration. CT responses increased in a dose-dependent manner to ∼0.3 M, whereafter they decreased with increasing concentration. At concentrations where Ca2+ was self-inhibitory, it also inhibited responses to NaCl, KCl, and NH4Cl present in mixtures with CaCl2. Ca2+ completely blocked the amiloride-insensitive component of the NaCl CT response, the entire KCl-evoked CT response, and the high-concentration-domain CT responses of NH4Cl (≥0.3 M). The overlapping Ca2+-sensitivity between the responses of the three Cl− salts (Na+, K+, and NH+ 4) suggests a common, Ca2+-sensitive, transduction pathway. Extracellular Ca2+ has been shown to modulate the paracellular pathways in different epithelial cell lines by decreasing the water permeability and cation conductance of tight junctions. Ca2+-induced modulation of tight junctions is associated with Ca2+ binding to fixed negative sites. This results in a conversion of ion selectivity from cationic to anionic, which we also observed in our system through simultaneous monitoring of the transepithelial potential during CT recording. The data indicate the paracellular pathway as the stimulatory and modulatory site of CaCl2 taste responses. In addition, they indicate that important transduction sites for NaCl, KCl, and NH4Cl taste reception are accessible only through the paracellular pathways. More generally, they show that modulation of paracellular transport by Ca2+ in an intact epithelium has functional consequences at a systemic level.

2021 ◽  
pp. 1-13
Author(s):  
Shu Wang ◽  
Xiang Li ◽  
Yue Yang ◽  
Jingping Xie ◽  
Mingyue Liu ◽  
...  

Abstract Objective: We aimed to evaluate the association between coffee and/or tea consumption and breast cancer (BC) risk among premenopausal and postmenopausal women and to conduct a network meta-analysis. Design: Systematic review and network meta-analysis. Setting: We conducted a systematic review of electronic publications in the last 30 years to identify case–control studies or prospective cohort studies that evaluated the effects of coffee and tea intake. Results: Forty-five studies that included more than 3 323 288 participants were eligible for analysis. Network meta-analysis was performed to determine the effects of coffee and/or tea consumption on reducing BC risk in a dose-dependent manner and differences in coffee/tea type, menopause status, hormone receptor and the BMI in subgroup and meta-regression analyses. According to the first pairwise meta-analysis, low-dose coffee intake and high-dose tea intake may exhibit efficacy in preventing ER(estrogen receptor)− BC, particularly in postmenopausal women. Then, we performed another pairwise and network meta-analysis and determined that the recommended daily doses were 2–3 cups/d of coffee or ≥5 cups/d of tea, which contained a high concentration of caffeine, particularly in postmenopausal women. Conclusions: Coffee and tea consumption is not associated with a reduction in the overall BC risk in postmenopausal women and is associated with a potentially lower risk of ER− BC. And the highest recommended dose is 2–3 cups of coffee/d or ≥5 cups of tea/d. They are potentially useful dietary protectants for preventing BC.


2021 ◽  
Vol 22 (11) ◽  
pp. 5978
Author(s):  
Hiroyuki Inoue ◽  
Hidetaka Kuroda ◽  
Wataru Ofusa ◽  
Sadao Oyama ◽  
Maki Kimura ◽  
...  

The ionotropic P2X receptor, P2X7, is believed to regulate and/or generate nociceptive pain, and pain in several neuropathological diseases. Although there is a known relationship between P2X7 receptor activity and pain sensing, its detailed functional properties in trigeminal ganglion (TG) neurons remains unclear. We examined the electrophysiological and pharmacological characteristics of the P2X7 receptor and its functional coupling with other P2X receptors and pannexin-1 (PANX1) channels in primary cultured rat TG neurons, using whole-cell patch-clamp recordings. Application of ATP and Bz-ATP induced long-lasting biphasic inward currents that were more sensitive to extracellular Bz-ATP than ATP, indicating that the current was carried by P2X7 receptors. While the biphasic current densities of the first and second components were increased by Bz-ATP in a concentration dependent manner; current duration was only affected in the second component. These currents were significantly inhibited by P2X7 receptor antagonists, while only the second component was inhibited by P2X1, 3, and 4 receptor antagonists, PANX1 channel inhibitors, and extracellular ATPase. Taken together, our data suggests that autocrine or paracrine signaling via the P2X7-PANX1-P2X receptor/channel complex may play important roles in several pain sensing pathways via long-lasting neuronal activity driven by extracellular high-concentration ATP following tissue damage in the orofacial area.


1990 ◽  
Vol 259 (4) ◽  
pp. H1032-H1037 ◽  
Author(s):  
T. Matsuki ◽  
T. Ohhashi

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.


Hypertension ◽  
2017 ◽  
Vol 70 (suppl_1) ◽  
Author(s):  
Minoru Isomura ◽  
Toru Nabika

Salt is an indispensable nutrient, but excessive amount of salt intake becomes harmful. In order to prevent excessive intake of salt, there is a mechanism to feel high concentration salt as an aversive taste. In recent years, it has clarified that high concentration salt stimulates different taste buds from those sensed by low concentration of salt. In this study, we analyzed relationship between inter-individual difference in sensitivity of aversive salt taste and amounts of daily salt intake. After obtained written informed consent, 1,254 individuals who came annual health checkups were recruited for this study. To test aversive salt taste, five different saline solutions (0.25%, 0.5%, 1%, 1.5%, 2%) were prepared. They started drinking of salt solution from low to high concentration of solutions. In each trial of drinking the salt solution, they were asked whether they were capable of drinking it. When they felt to avoid drinking the salt solution, salt concentration of the solution was recorded as sensitivity of aversive salt taste. Amount of daily salt intake was estimated by using spot urine and by dietary questionnaire. As a result, 784(63%) and 267(21 %) of individuals felt up to the 1.5% and 2% of salt solution as aversive salt taste, respectively. Hence, their sensitivities of aversive salt taste were 1.5% or 2% of salt solutions, respectively. However, resting 203(16%) of individuals showed capability to drink 2% of salt solution. Although we compared sensitivities of aversive salt taste of each individual and daily salt intake that estimated by urine, there were no difference between them. However, daily salt intake that estimated by dietary questionnaire showed clear relationship, in which individuals with the high sensitivities of aversive salt taste consumed the more amount of salt.


Materials ◽  
2019 ◽  
Vol 12 (7) ◽  
pp. 1150 ◽  
Author(s):  
Jinxin Liu ◽  
Lanqing Yu ◽  
Min Deng

The aim of this research is to investigate the effect of LiNO3 on the alkali–silica reaction (ASR) expansion of reactive sandstone and the mechanism through which this occurs. This paper presents the results from tests carried out on rock prisms and concrete microbars prepared by sandstone and LiNO3. The findings show that LiNO3 does not decrease the expansion of these samples unless the molar ratio of [Li]/[Na + K] exceeds 1.66, and the expansion is greatly increased when its concentration is below this critical concentration. The expansion stress test proves that Li2SiO3 is obviously expansive. X-ray diffraction (XRD) and scanning electron microscope (SEM) results indicate that LiNO3 reacts with the microcrystalline quartz inside sandstone, inhibiting the formation of ASR gel, and the formation of Li2SiO3 causes larger expansion. A high concentration of LiNO3 might inhibit the ASR reaction in the early stages, and the formation of Li2SiO3 causes expansion and cracks in concrete after a long period of time.


2018 ◽  
Vol 3 (1) ◽  
pp. 3 ◽  
Author(s):  
Leszek Ruchomski ◽  
Edward Mączka ◽  
Marek Kosmulski

We studied the behavior of dilute dispersions of nanoparticles of hematite, alumina, and titania in the presence of various concentrations of very pure sodium dodecyl-, tetradecyl-, and hexadecylsulfate. The concentrations studied were up to critical micelle concentration (CMC) for sodium dodecylsulfate, and up to the solubility limit in case of sodium tetradecyl- and hexadecylsulfate. The dispersions were adjusted to different pH (3–11), and 10−3 M NaCl was used as the supporting electrolyte. The solid-to-liquid ratio was strictly controlled in all dispersions, and the behavior of fresh dispersions was compared with dispersions aged for up to eight days. The presence of very low concentrations of ionic surfactants had rather insignificant effects on the ζ potentials of the particles. At sufficient concentrations of ionic surfactants the isoelectric point (IEP) of metal oxides shifted to low pH, and the long-chain surfactants were more efficient in shifting the IEP than their shorter-chain analogues. Once the surfactant concentration reached a critical value, the ζ potentials of the particles reached a pH-independent negative value, which did not change on further increase in the surfactant concentration and/or aging of the dispersion. This critical concentration increases with the solid-to-liquid ratio, and it is rather consistent (for certain oxides and certain surfactants) when it is expressed as the amount of surfactant per unit of surface area. Surprisingly, the surfactant-stabilized dispersions always showed a substantial degree of aggregation; that is, the particle size observed in dispersions by dynamic light scattering was higher than the size of particles observed in dry powders by electron microscopy. Apparently, in spite of relatively high ζ potentials (about 60 mV in absolute value), the surfactant-stabilized dispersions consist of aggregates rather than of primary particles, and in certain dispersions the high concentration of surfactant seems to induce aggregation rather than prevent it.


1997 ◽  
Vol 273 (6) ◽  
pp. R1923-R1931 ◽  
Author(s):  
Robert F. Lundy ◽  
David W. Pittman ◽  
Robert J. Contreras

The effects of the epithelial Na+channel antagonists amiloride and benzamil and the Na+/H+exchange antagonist 5-( N, N-dimethyl)-amiloride (DMA)-Cl on the integrated responses of the chorda tympani nerve to 30, 75, 150, 300, and 500 mM concentrations of NaCl, KCl, and NH4Cl were assessed in male Sprague-Dawley rats. Based on evidence from other systems, 1 and 25 μM amiloride and benzamil were chosen to selectively inhibit epithelial Na+ channels and 1 μM DMA was chosen to selectively inhibit Na+/H+exchange. When added to stimulating salt solutions, amiloride, benzamil, and DMA were each effective in inhibiting responses to all three salts. The degree of inhibition varied with drug, salt, and salt concentration, but not drug dose. Amiloride suppressed NaCl responses to a greater degree than KCl and NH4Cl responses, whereas DMA suppressed NH4Cl responses to a greater degree than NaCl and KCl responses. In all but one case (25 μM amiloride added to KCl), drug suppression of taste nerve responses decreased with an increase in salt concentration. The present results suggest that 1) epithelial Na+ channels in rat taste receptor cells may play a role in KCl and NH4Cl taste transduction; 2) a Na+/H+exchange protein may be present in taste receptor cells, representing a putative component, in addition to epithelial Na+ channels, in salt taste transduction; and 3) salt taste detection and transduction may depend on the utilization of a combination of common and distinct transcellular pathways.


1998 ◽  
Vol 275 (5) ◽  
pp. C1201-C1206 ◽  
Author(s):  
Kouhei Inamura ◽  
Makoto Kashiwayanagi ◽  
Kenzo Kurihara

The effects of cGMP and sodium nitroprusside (SNP) on odor responses in isolated turtle olfactory neurons were examined. The inward current induced by dialysis of a mixture of 1 mM cAMP and 1 mM cGMP was similar to that induced by dialysis of 1 mM cAMP or 1 mM cGMP alone. After the neurons were desensitized by the application of 1 mM cGMP, 3 mM 8-(4-chlorophenylthio)-cAMP, a membrane-permeable cAMP analog, did not elicit any current, indicating that both cAMP and cGMP activated the same channel. Extracellular application of SNP, a nitric oxide (NO) donor, evoked inward currents in a dose-dependent manner. However, application of SNP did not induce any currents after desensitization of the cGMP-induced currents, suggesting that SNP-induced currents are mediated via the cGMP-dependent pathway. Application of the cAMP-producing odorants to the neurons induced a large inward current even after neurons were desensitized to a high concentration of cGMP or SNP. These results suggest that the transduction pathway independent of cAMP, cGMP, and NO also contributes to the generation of odor responses in addition to the cAMP-dependent pathway.


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