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 28,634 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Stimulation with extracellular ATP causes a rapid initial transient rise followed by asynchronous periodic oscillations in cytosolic calcium ion activity ([Ca2+]i) in individual aortic smooth muscle cells in either HEPES-buffered or HCO3(-)-buffered saline. The dose at which one-half of the cells display an initial rise in cytosolic calcium is 0.11 microM ATP in the presence of external Ca2+ and 0.88 microM ATP in the absence of external Ca2+; the corresponding value for oscillations in the presence of external Ca2+ is 2.6 microM ATP. While the initial transient displays rapid desensitization, the oscillations persist for greater than 30 min in the continuous presence of ATP. The presence of the agonist ATP is also absolutely required for the maintenance of the oscillations, presumably to provide continuous activation of P2 purinoceptors. The average frequency of oscillation is approximately 0.9 min-1. The frequency depends only slightly on the concentration of ATP, and oscillations do not collapse into a prolonged elevated [Ca2+]i at high concentrations of ATP. Both Ca2+ influx and release from internal stores participate in the initial transient. Oscillations are not produced in the absence of external Ca2+ but are initiated upon the addition of external Ca2+ in the continued presence of ATP. Oscillations in progress are abolished by the removal of extracellular Ca2+ with one additional peak occurring after the Ca2+ removal. These data suggest that extracellular Ca2+ influx is required for the maintenance of the posttransient oscillations, presumably to provide the Ca2+ necessary for refilling intracellular Ca2+ pools that are the source of the oscillating [Ca2+]i. The Ca2+ influx is not regulated by voltage-gated Ca2+ channels. The data in this report are consistent with the view that the initial transient has contributions from two receptor-mediated pathways, and the oscillations are controlled either by a mechanism separate from the ones that control the initial transient or by steps whose control diverges before the point of desensitization.
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PMID:Independent pathways regulate the cytosolic [Ca2+] initial transient and subsequent oscillations in individual cultured arterial smooth muscle cells responding to extracellular ATP. 131 42

Regulation of intracellular pH (pHi) in single cultured rat hippocampal neurons was investigated using the fluorescent pHi indicator dye bis-carboxyethylcarboxyfluorescein. Resting pHi was dependent on the presence of bicarbonate and external Na+ but was not altered significantly by removal of Cl- or treatment with the anion exchange inhibitor diisothiocyanatostilbene-2,2'-disulfonate. Recovery of pHi from acute acid loading was due, in large part, to a pharmacologically distinct variant of the Na+/H+ antiporter. In nominally HCO3(-)-free solutions, this recovery exhibited a saturable dose dependence on extracellular Na+ (Km = 23-26 mM) or Li+. The antiporter was activated by decreasing pHi and was unaffected by collapse of the membrane potential with valinomycin. Like the Na+/H+ antiporter described in other cell systems, the hippocampal activity was inhibited by harmaline, but in sharp contrast, neither amiloride nor its more potent 5-amino-substituted analogues were able to prevent the recovery from an acid load. These data indicate that Na(+)-dependent mechanisms dominate pHi regulation in hippocampal neurons and suggest a role for a novel variant of the Na+/H+ antiporter.
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PMID:Regulation of intracellular pH in cultured hippocampal neurons by an amiloride-insensitive Na+/H+ exchanger. 184 31

A case of severe lithium carbonate self-poisoning is described, presenting with a very high serum lithium level (14.6 mmol/L) on admission. Lengthy and repeated hemodialyses were required to lower lithemia to nontoxic ranges. As is usually reported, our patient had prolonged neurologic manifestations (coma, hyperreflexia, fluctuating focal signs) and developed hypotension, cardiovascular collapse, nephrogenic diabetes insipidus, and diarrhea. Other less common features were the occurrence of acute myocardial infarction without coronary artery lesions and thrombocytopenia. The possible pathogenic mechanisms are discussed. Hemodialysis and supportive intensive care treatment are commented upon. The final outcome was favorable, and the patient recovered completely.
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PMID:Very severe self-poisoning lithium carbonate intoxication causing a myocardial infarction. 190 21

Membrane transport pathways for transplacental transfer of CO2/HCO3 were investigated by assessing the possible presence of a Cl/HCO3 exchange mechanism in the maternal-facing membrane of human placental epithelial cells. Cl/HCO3 exchange was tested for in preparations of purified brush border membrane vesicles by 36Cl tracer flux measurements and determinations of acridine orange fluorescence changes. Under 10% CO2/90% N2 the imposition of an outwardly directed HCO3- concentration gradient (pHo 6/pHi 7.5) stimulated Cl- uptake to levels approximately 2-fold greater than observed at equilibrium. Maneuvers designed to offset the development of ion gradient-induced diffusion potentials (valinomycin, Ko = Ki) significantly reduced HCO3- gradient-driven Cl- uptake but concentrative accumulation of Cl- persisted. Early time point determinations performed in the presumed absence of membrane potential suggests the reduced level of HCO3- gradient-driven Cl- uptake resulted from a more rapid dissipation of the HCO3- concentration gradient. Concentrative accumulation of Cl- was not observed in the presence of a pH gradient alone under 100% N2, suggesting a preference of HCO3- over OH- as a substrate for transport. As monitored by acridine orange fluorescence the Cl- gradient-dependent collapse of an imposed pH gradient (pHo 8.5/pHi 6) was accelerated in the presence of CO2/HCO3 when compared with its absence, indicating coupling of HCO3- influx to Cl- efflux. Increasing concentrations of the anion exchange inhibitor 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid were observed to cause a stepwise reduction in HCO3- gradient-driven Cl- uptake (I50 approximately 25 microM) further suggesting the presence of a Cl/HCO3 exchange mechanism. The results of this study provide evidence for a 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid-sensitive Cl/HCO3 exchange mechanism in the maternal-facing membrane of human placental epithelial cells. The identification of an ion-coupled HCO3- transport pathway in placental epithelia may suggest functional roles in mediating transplacental transfer of CO2 as well as maintenance of fetal acid/base balance.
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PMID:C1/HCO3 exchange in human placental brush border membrane vesicles. 273 59

We evaluated the effects of acetazolamide on Na+-HCO3- cotransport in basolateral membrane vesicles isolated from the rabbit renal cortex. Na+ uptake stimulated by an imposed inward HCO3- gradient was not significantly reduced by 1.2 mM acetazolamide, indicating that acetazolamide does not directly inhibit Na+-HCO3- cotransport. 4,4'-Diisothiocyanostilbene-2,2'-disulfonate (DIDS)-sensitive Na+-base cotransport was found to be absolutely CO2/HCO3--dependent. We therefore tested whether acetazolamide-sensitive availability of HCO3- at the basolateral membrane could be rate-limiting for Na+-base cotransport under some conditions. In the presence of a CO2/HCO3- buffer system but absence of an initial HCO3- gradient, Na+ influx was stimulated fivefold by an outward NH4+ gradient. This stimulation of Na+ influx by an outward NH4+ gradient was inhibited greater than 75% by 0.6 mM acetazolamide, suggesting that acetazolamide blocked the ability of the NH4+ gradient to generate an inward HCO3- gradient. In the presence of an inward HCO3- gradient, Na+ influx was inhibited greater than 70% by an inward NH4+ gradient. This inhibition of Na+ influx was reduced to only 35% by 0.6 mM acetazolamide, suggesting that acetazolamide blocked the ability of NH4+ to collapse the inward HCO3- gradient. Similarly, Na+ influx in the presence of an inward HCO3- gradient was inhibited greater than 80% by an outward acetate gradient, and this inhibition was reduced to only 50% by acetazolamide. Thus, acetazolamide caused either inhibition or stimulation of Na+ uptake depending on the conditions with respect to pH and HCO3- gradients. The indirect interaction of acetazolamide with the basolateral membrane Na+-HCO3- cotransport system may be an important mechanism underlying inhibition of proximal tubule acid secretion by this agent.
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PMID:Effects of acetazolamide on Na+-HCO-3 cotransport in basolateral membrane vesicles isolated from rabbit renal cortex. 292 27

A 65-year-old female presented with only gastrointestinal symptoms eight to ten hours after an acute ingestion of an unknown amount of lithium carbonate. The serum lithium concentration was 8.5 mEq/L. Forty-eight hours postingestion she developed acute renal failure, deteriorating mental status, and cardiovascular collapse. Despite both hemodialysis and peritoneal dialysis the patient died approximately four and one-half days after ingestion. A direct nephrotoxic effect of lithium is proposed.
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PMID:Lithium intoxication with acute renal failure and death. 321 11

Small deformation oscillatory rheologic measurements have been used to investigate the structure of human and pig gastric mucus and pig duodenal mucus. All three secretions had viscoelastic properties characteristic of water-insoluble, viscoelastic gels. Mucus will flow and anneal if damaged, due to the making and breaking of its elastic structure, the measured lifetime of which was 10-120 min. Mucus reconstituted by concentration of the purified glycoprotein (pig gastric and duodenal mucus) had the same viscoelastic properties as the fresh mucus, giving evidence that the glycoprotein alone will reproduce the rheologic characteristics of the mucus. The structure of fresh mucus gel was unaffected by prolonged exposure to the following mucosal damaging agents: undiluted pig bile, 20 mM sodium taurocholate or 20 mM sodium glycocholate (all at pH 2, 6, and 8), HCl at pH 1, 2 M NaCl, and ethanol less than 40% (vol/vol). Higher concentrations of ethanol greater than 40% (vol/vol), caused dehydration and denaturation of mucus. Proteolysis by pepsin and other enzymes resulted in solubilization of the mucus gel with a complete change in the properties from an "elastic" gel to those of a "viscous" liquid. A similar collapse of mucus gel structure was observed after reduction of disulfide bonds in 0.2 M mercaptoethanol, but only after incubation for at least 50 min. This study demonstrates the stability of mucus to several mucosal damaging agents. It is proposed in vivo that although adherent gastroduodenal mucus allows penetration of these agents to the underlying mucosa, it can remain in situ and continue to protect against acid (with HCO3-) and pepsin, thus minimizing mucosal damage and maximizing repair.
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PMID:Properties of gastric and duodenal mucus: effect of proteolysis, disulfide reduction, bile, acid, ethanol, and hypertonicity on mucus gel structure. 391 63

On the basis of experiments with primary cultures of mouse astrocytes with conventional K(+)-sensitive intracellular microelectrodes involving 'chemical ischemia' (antimycin a and sodium fluoride treatment), a model of ischemia is presented. According to this model, ischemia has no significant direct effect during the first 10 min on astrocytes; neurones, however, lose a major part of their K+ into the ECS. This leads to an astrocytic depolarization, which in turn activates astrocytic anion channels. This will result in passive, Donnan-mediated K+, Cl- and HCO3- fluxes into astrocytes, which in turn causes swelling and a collapse of the ECS. Arguments are put forward that this may explain the swelling of astrocytic endfeet, which occurs very early in an ischemic insult.
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PMID:Glial swelling in ischemia: a hypothesis. 780 73

The barrier that protects the undamaged gastroduodenal mucosa from autodigestion by gastric juice is a dynamic multicomponent system. The major elements of this barrier are the adherent mucus gel layer, which is percolated by the HCO3- secretion from the underlying epithelial cells; the epithelial layer itself, which provides a permeability barrier and can rapidly repair superficial damage by a process of cell migration referred to as reepithelization or restitution; and a specially adapted vasculature, which provides a supply of HCO3- for transcellular transport and/or diffusion into the mucus layer. Passive diffusion of intestinal HCO3- into the lumen is particularly important when there is superficial damage resulting in increased leakiness of the mucosal epithelium. The process of reepithelization occurs by the migration of performed cells from gastric pits or duodenal crypts. This process is quite distinct from the wound healing and associated inflammatory response that accompany more severe injury or chronic damage. The adherent mucus gel acts as a physical barrier against luminal pepsin and provides a stable unstirred layer that supports surface neutralization of acid by mucosal HCO3-. Surface neutralization by mucosal HCO3- provides a major mechanism of protection against acid in the proximal duodenum. In the stomach, where luminal acidity can fall to around pH 1, other mechanisms of protection must exist, since the surface pH gradient is reported to collapse when luminal H+ exceeds approximately 10 mM. This collapse of the surface pH gradients may reflect, at least in part, that such studies have been mostly performed on non-acid-secreting mucosa where the supply of HCO3- to the interstitium from the parietal cells will be reduced. However, because the gastric mucosa can withstand prolonged exposure to acid without apparent damage, this implies an intrinsic resistance of the epithelial apical surface. This is amply illustrated within the gastric glands that do not secrete mucus and HCO3- yet are exposed to undiluted pepsin and an isotonic solution of HCl. Bicarbonate and mucus secretions together with mucosal blood flow are under paracrine, endocrine, and neural control. The rate of reepithelialization will depend on local chemotactic factors, adhesion mechanisms, and the creation of an acid/pepsin/irritant-free environment under a protective gelatinous or mucoid cap. If optimal conditions are met, then the rate of reepithelialization appears to depend primarily on the intrinsic properties of the migrating cells themselves rather than control by exogenous mediators.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Gastroduodenal mucosal protection. 841 27

Collapsed proximal convoluted tubules (PCT) shrink to reach a volume 20% lower than control and do not exhibit regulatory volume increase when submitted to abrupt 150 mOsm/kg hypertonic shock. The shrinking is accompanied by a rapid depolarization of the basolateral membrane potential (VBL) of 8.4 +/- 0.5 mV, with respect to a control value of -54.5 +/- 1.9 mV (n = 15). After a small and transient hyperpolarization, VBL further depolarizes to reach a steady depolarization of 19.5 +/- 1.5 mV (n = 15) with respect to control. In the post-control period, VBL returns to -55.8 +/- 1.5 mV. The basolateral partial conductance to K+ (tK) which is 0.17 +/- 0.01 (n = 5) in control condition, decreases rapidly to nonmeasurable values during the hypertonic shock and returns to 0.23 +/- 0.03 in the post-control period. The basolateral partial conductance to Cl- (tCl), which is 0.05 +/- 0.02 (n = 5) in control, also decreases in hypertonicity to a nonmeasurable value and returns to 0.03 +/- 0.01 in post control. The partial conductance mediated by the Na-HCO3 cotransporter (tNaHCO3), which is 0.48 +/- 0.06 (n = 5) in control condition, remains the same at 0.44 +/- 0.05 (n = 5) during the hypertonic period. Similarly, the membrane absolute conductance mediated by the Na-HCO3 cotransporter (GNa-HCO3) does not vary appreciably. Concomitant with cell shrinkage, intracellular pH (pHi) decreases from a control value of 7.26 +/- 0.01 to 7.13 +/- 0.02 (n = 12) and then remains constant. Return to control solution brings back pHi to 7.28 +/- 0.03. From these results, we conclude that in collapsed PCT, a sustained decrease in cellular volume leads to cell acidification and to inhibition of K+ and Cl- conductances.
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PMID:Hypertonicity decreases basolateral K+ and Cl- conductances in rabbit proximal convoluted tubule. 905 Apr 46


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