Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: CAS:7440-70-2 (calcium)
 333,191 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of clanobutin (4-[4-chloro-N-(4-methoxyphenyl)-benzamido]butyric acid) were investigated on two in vitro pancreatic preparations. In rat pancreatic lobules clanobutin (7.2 mM) stimulated the secretion of amylase and radiolabeled proteins to the same or higher extent as did CCK-PZ and carbachol in maximally active doses, but with a delay of 1-2 h. In the isolated rabbit pancreas clanobutin (3.3 mM) stimulated protein secretion about half as much as did carbachol, but without significant delay. The effect of clanobutin on protein secretion was prevented by prior application of carbachol, was not affected by the omission of Ca2+ from the medium and was only partly inhibited by the presence of atropine (0.1 mM). Prior addition of clanobutin did not prevent the effects of carbachol on enzyme secretion. In addition, clanobutin (3.3 mM) inhibited fluid secretion in the rabbit pancreas by about 50 percent; the inhibition was reversible. No effects on paracellular permeability were found with sucrose used as test substance. The findings indicate that clanobutin has opposite effects on enzyme and fluid secretion by rat and rabbit pancreas, which are not due to circulatory effects.
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PMID:Effects of clanobutin on pancreatic secretion in vitro. 617 May 19

Adrenaline causes a dose-related increase in enzyme (lactate dehydrogenase) release from the isolated perfused working rat heart and a rise in tissue cAMP. Rates of both enzyme release and tissue cAMP fell with beta blockade by propranolol (plus pacing to maintain heart rate). Theophylline also increased enzyme release and tissue cAMP. Dibutyryl cAMP, but not butyric acid or external cAMP, increased enzyme release. Hence the release of enzyme is mediated by cAMP according to the criteria of Sutherland et al (11) for mediating the action of catecholamines. However, factors other than cAMP are operative because the extent of enzyme release and the tissue cAMP can be dissociated by variations in external calcium or magnesium or glucose, which modulate the effects of a given level of cAMP.
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PMID:Cyclic AMP as mediator of catecholamine-induced enzyme release from isolated perfused working rat heart. 624 40

K+ fluxes of rat cortical synaptosomes were monitored by a K+ sensitive ion-selective membrane electrode. The uptake phases of K+curves from control and experimental measurements were compared and statistically evaluated. GABA significantly reduced K+ uptake but it was able to reverse the decrease of K+ uptake caused by protoveratrine. In the absence of Ca2+ the K+ uptake was diminished; GABA had no effect on this inhibition. The effect of GABA on K+ take was partially reduced by bicuculline and abolished by diamino-butyric acid. The K+ content of synaptosomes decreased, while the NA+ content increased in the presence of GABA. The results are discussed in association with presynaptic depolarisation and with modulatory effects of GABA on the release of other transmitters.
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PMID:The effect of gamma-aminobutyric acid on the potassium movements of rat cortical synaptosomes. 627 25

Rat pituitary neural lobe contained high concentrations of cholecystokinin-like immunoreactivity (CCK-LI). Section of the pituitary stalk resulted in loss of CCK-LI, and both lactation and replacement of drinking water with 2% saline resulted in marked depletion of CCK-LI. Rats with congenital diabetes insipidus (Brattleboro strain) had a 73% reduction in CCK-LI below the levels of hooded Long-Evans controls, where as levels in the brain were unchanged. Release of CCK-LI, labeled dopamine, and gamma-amino butyric acid in response to potassium depolarization was studied. There was a low fractional release of CCK-LI. Addition of sulfated CCK-8 (CCK-8s) to the medium enhanced the calcium-dependent potassium-stimulated release of dopamine, but basal release was unaffected. gamma-Amino butyric acid release was only poorly calcium dependent and not effected by extracellular CCK-8s. Vasopressin and oxytocin release were stimulated by electrical stimulation of the pituitary stalk, and were unaffected by the addition of CCK-8s to the medium. In vivo, however, the injection of 5 micrograms CCK-8s into the third ventricle resulted in increased plasma vasopressin concentrations.
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PMID:Localization and actions of cholecystokinin in the rat pituitary neurointermediate lobe. 632 36

Parallel changes in the enzyme activities of CA2+ATPase and alkaline phosphatase were observed in HeLa cells. Both enzymes were inhibited to a similar degree by L-phenylalanine, L-tryptophan, and L-leucine, while being relatively resistant to L-homoarginine. Exposure to heat (56 degrees C, 60 degrees C, and 65 degrees C) resulted in a loss of both enzyme activities. Both alkaline phosphatase and Ca2+ ATPase, when treated with EGTA, required Ca2+ for the restoration of activity. Cells grown in the presence of agents that affect alkaline phosphatase (dexamethasone, butyric acid, and hyperosmolar NaCl) showed similar changes in the activities of both enzymes.
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PMID:Similarities between alkaline phosphatase and Ca2+ ATPase activities in HeLa cells. 645 Jul 71

A key event in the initiation of the dimethyl sulfoxide (DMSO)-induced program of murine erythroleukemia (MEL) cell differentiation is a rise in the level of cytoplasmic calcium ions. Our interest in the present study is whether other inducers of the terminal erythroid differentiation program also act via a calcium-dependent pathway. Inhibition of calcium transport has been found to prevent the induction of MEL cell commitment by DMSO, butyric acid (BA), or hypoxanthine (HX). Enhancement of the calcium flux rate with A23187 or elevation of cytoplasmic calcium levels with FCCP stimulates the kinetics of commitment in response to all three inducers. These results suggest that of the inducers we have tested (DMSO, BA, and HX), all three act to initiate commitment via a common mechanism which involves modulation of cytoplasmic calcium levels.
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PMID:Ionic regulation of MEL cell commitment. 657 72

The present study was intended to investigate whether voltage- and ligand-activated ion channels are expressed during prenatal development by neurones located in the ganglion cell layer of the mammalian retina. Whole cell patch clamp recordings from presumed mouse retinal ganglion cells revealed the expression of Na+, K+ and Ca2+ channels, predominantly of the low-voltage-activated type. Using local application of transmitter substances we further demonstrated that these cells are endowed with glutamate receptors of the N-methyl-D-aspartate (NMDA) and non-NMDA type as well as nicotinic acetylcholine, gamma-amino-butyric acid (GABA)A and glycine receptors. Voltage-gated conductances probably underlie spontaneous action potential generation by embryonic ganglion cells. The early expression of transmitter-gated ion channels indicates important functions of these channels in cell differentiation processes.
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PMID:Ligand- and voltage-gated ion channels are expressed by embryonic mouse retinal neurones. 752 9

This overview of the potential mechanisms of chemopreventive activity will provide the conceptual groundwork for chemopreventive drug discovery, leading to structure-activity and mechanistic studies that identify and evaluate new agents. Possible mechanisms of chemopreventive activity with examples of promising agents include carcinogen blocking activities such as inhibition of carcinogen uptake (calcium), inhibition of formation or activation of carcinogen (arylalkyl isothiocyanates, DHEA, NSAIDs, polyphenols), deactivation or detoxification of carcinogen (oltipraz, other GSH-enhancing agents), preventing carcinogen binding to DNA (oltipraz, polyphenols), and enhancing the level or fidelity of DNA repair (NAC, protease inhibitors). Chemopreventive antioxidant activities include scavenging reactive electrophiles (GSH-enhancing agents), scavenging oxygen radicals (polyphenols, vitamin E), and inhibiting arachidonic acid metabolism (glycyrrhetinic acid, NAC, NSAIDs, polyphenols, tamoxifen). Antiproliferation/antiprogression activities include modulation of signal transduction (glycyrrhetinic acid, NSAIDs, polyphenols, retinoids, tamoxifen), modulation of hormonal and growth factor activity (NSAIDs, retinoids, tamoxifen), inhibition of aberrant oncogene activity (genistein, NSAIDs, monoterpenes), inhibition of polyamine metabolism (DFMO, retinoids, tamoxifen), induction of terminal differentiation (calcium, retinoids, vitamin D3), restoration of immune response (NSAIDs, selenium, vitamin E), enhancing intercellular communication (carotenoids, retinoids), restoration of tumor suppressor function, induction of programmed cell death (apoptosis) (butyric acid, genistein, retinoids, tamoxifen), correction of DNA methylation imbalances (folic acid), inhibition of angiogenesis (genistein, retinoids, tamoxifen), inhibition of basement membrane degradation (protease inhibitors), and activation of antimetastasis genes. A systematic drug development program for chemopreventive agents is only possible with continuing research into mechanisms of action and thoughtful application of the mechanisms to new drug design and discovery. One approach is to construct pharmacological activity profiles for promising agents. These profiles are compared among the promising agents and with untested compounds to identify similarities. Classical structure-activity studies are used to find optimal agents (high efficacy with low toxicity) based on good lead agents. Studies evaluating tissue-specific and pharmacokinetic parameters are very important. A final approach is design of mechanism-based assays and identification of mechanism-based intermediate biomarkers for evaluation of chemopreventive efficacy.
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PMID:Mechanistic considerations in chemopreventive drug development. 761 36

The colocalization of two calcium-binding proteins, parvalbumin (PV) and calbindin-D28k (CaB), which have been reported to be markers of specific subpopulations of neurons in the central nervous system, with the inhibitory amino acid neurotransmitter gamma-amino-butyric acid (GABA) was investigated in neurons of laminae I-IV of the subnucleus caudalis of the rat spinal trigeminal nucleus by using post-embedding immunocytochemical methods. Cells immunoreactive for PV, CaB, and GABA were found in all four laminae of the subnucleus caudalis. A substantial proportion of PV-immunoreactive perikarya were also stained for GABA in laminae II and III (44.8% and 39.8%, respectively). However, the majority of PV-containing neurons in laminae I and IV (100% and 86%, respectively), as well as CaB-immunoreactive cells in all four laminae (98.4%), were GABA-negative. These results show that, in contrast to higher brain centers, PV-, CaB-, and GABA-immunoreactive perikarya represent significantly different populations of neurons in the subnucleus caudalis of the rat. In the light of the present findings, the differences in the neurochemical properties of the subnucleus caudalis of the spinal trigeminal nucleus and the spinal dorsal horn are also discussed.
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PMID:The colocalization of parvalbumin and calbindin-D28k with GABA in the subnucleus caudalis of the rat spinal trigeminal nucleus. 778 46

The purpose of this study was to evaluate potential mechanisms of ischemia-evoked amino acid transmitter release. Changes in extracellular levels of transmitter amino acids and lactic acid dehydrogenase (LDH) in rat cerebral cortex during and following four-vessel occlusion elicited global cerebral ischemia were examined using a cortical cup technique. Ischemia-evoked release of glutamate, aspartate and gamma-amino-butyric acid (GABA) was compared in control vs. drug-treated animals. Tetrodotoxin and antagonists of glutamate receptors (DNQX, MK-801, and AP-3) depressed the initial rate of increase in extracellular glutamate and aspartate without altering the total amount of these amino acids collected in the cortical superfusates. Cobalt, a calcium channel antagonist, failed to alter efflux. Acidic amino acid transport inhibitors (dihydrokainate, L-trans-PDC) depressed the rate of onset of glutamate and aspartate release and dihydrokainate depressed total release by 44%. PD 81723, an allosteric enhancer at the A1 adenosine receptor, depressed glutamate efflux, as did L-NAME, an inhibitor of nitric oxide synthase. Extracellular increases in GABA levels were depressed by tetrodotoxin and L-trans-PDC. The GABA transport inhibitor, nipecotic acid, increased the initial rate of onset of GABA release. Increases in LDH levels in the extracellular fluid became apparent during the period of ischemia and continued to increase during the subsequent 90 min of reperfusion. These results suggest that ischemia evokes a release of neurotransmitter amino acids that is only partially dependent upon Ca2+ influx activation or the reversal of amino acid transporters. Nonselective mechanisms, resulting from the disruption of plasma membrane integrity, may contribute significantly to the total ischemia-evoked release of excitatory amino acids.
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PMID:Characterization of glutamate, aspartate, and GABA release from ischemic rat cerebral cortex. 791 62


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