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S Medrano

Publications and source records attributed to S Medrano.

10 recordsLinked to original sources
PubMed1994

Substance P receptors on human astrocytoma cells are linked to glycogen breakdown.

In this study we report that substance P stimulated [3H]glycogen breakdown and elevation of intracellular Ca2+ concentration in the human astrocytoma cell line UC-11MG. Both effects were dose dependent, and completely blocked by CP-96,345 suggesting the involvement of an NK1 receptor. Our previous studies indicated that norepinephrine and histamine stimulate glycogenolysis via cAMP and Ca2+ respectively. Combined stimulation with substance P and norepinephrine or histamine resulted in additive effects suggesting that there is no interaction between these neurotransmitters in regulating glycogenolysis in these cells. These results confirm that UC-11MG cells are a useful model system to investigate the functional role of neurotransmitter receptors in astroglial cells.

Astrocytoma↗
PubMed1993

Mechanisms of regulatory volume decrease in UC-11MG human astrocytoma cells.

Swelling of astrocytes commonly occurs after cerebral ischemia and other brain injuries. Because these cells constitute 20-25% of human brain volume, their swelling is a major factor in the morbidity and mortality associated with cerebral edema. Many cells, including astrocytes, resist or reverse the tendency to swell by activating transport pathways that lead to a regulatory volume decrease. Here we report the results of studies designed to elucidate the mechanisms of the regulatory volume decrease that occurs after astrocytes are swollen by exposure to hypotonic medium. Using UC-11MG cells, a well-characterized, human, astrocytoma-derived line, we observed an increase in membrane permeability to both K+ and Cl- during regulatory volume decrease, consistent with a net loss of these ions. Neither the increase in K+ exit nor the regulatory volume decrease was affected by bumetanide, an inhibitor of anion-cation cotransport. On the other hand, the increased K+ efflux, as well as the regulatory volume decrease, was blocked by Gd3+, suggesting a putative role of stretch-activated cationic channels in the process of volume regulation. Although increases in intracellular free Ca2+ were also observed during hypotonic treatment, they occurred well after the onset of the regulatory volume decrease. Furthermore, the regulatory volume decrease was not affected by blocking the intracellular free Ca2+ increase with dimethyl 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid or by removal of extracellular Ca2+. These results indicate that the regulatory volume decrease in UC-11MG cells may involve stretch-activated channels that operate independently of changes in intracellular free Ca2+.

Astrocytes↗
PubMed1992

Histamine stimulates glycogenolysis in human astrocytoma cells by increasing intracellular free calcium.

Astrocytes from a variety of sources, including the human UC-11MG astrocytoma line, express receptors for histamine on their plasma membranes, but the function of these receptors is largely unknown. Here we report studies on the effect of histamine on newly synthesized glycogen in the human astrocytoma-derived cell line, UC-11MG. We have found [3H]glycogen hydrolysis with a EC50 of 2 microM and a maximum effect of 30% at 300 microM histamine. The glycogenolytic effect of histamine was completely blocked by the H1 receptor antagonist, mepyramine, and was insensitive to the H2 receptor antagonist, cimetidine. Histamine-induced glycogenolysis was significantly reduced in the absence of extracellular Ca2+ and the residual response could be accounted for by Ca2+ released from intracellular stores. The Ca2+ ionophore, ionomycin, induced a similar concentration-dependent increase in both intracellular Ca2+ concentration and in glycogenolysis. These results suggest that one function of astrocytic histamine receptors in vivo may be the stimulation of glucose release from astrocytes, and that this process is mediated by increased intracellular free Ca2+. The glycogenolytic effect of histamine and other neurotransmitters in different systems, and the possible implication of astrocytic glycogenolysis in the pathophysiology of ischemia are discussed.

Astrocytoma↗
PubMed1990

Characteristics of a presynaptic plasma membrane Ca2(+)-ATPase activity from electric organ.

Ca2(+)-ATPase activity was measured in electric organ synaptosomal homogenates and their derived presynaptic plasma membranes using a low ionic strength medium, low in Ca2+ and Mg2+, and devoid of K+. The enzyme activity showed a high apparent affinity for Ca2+ (KCa:0.5 microM) and was: (1) 5-fold stimulated by 120 nM calmodulin, (2) highly sensitive to LaCl3 inhibition, and (3) not affected by 20 mM NaN3 or 0.1 mM ouabain. The addition of Mg2+ promoted the disappearance of Ca2(+)-ATPase activity. Incubation of synaptosomal homogenates in the above-mentioned assay medium with [gamma -32P]ATP resulted in the appearance of a 140 kDa band as revealed by SDS-gel electrophoresis. Labeling of this band with 32P was inhibited by 1 mM EGTA or 10 mM NH2OH, indicating that the isotope incorporation required the presence of Ca2+ and the formation of an acyl-phosphate derivative. The results indicate that the Ca2(+)-ATPase activity from synaptosomal homogenates had characteristics corresponding to those of the enzyme that catalyzes an outward transport of Ca2+ in nerve terminals. Preincubation of synaptosomes in Ca2+ plus K+, a depolarizing procedure, induced a large and rapid decrease in the Ca2(+)-ATPase activity, possibly mediated via Ca2+ entry through voltage-gated Ca2+ channels. Furthermore, the muscarinic cholinergic agonist oxotremorine (at 15 microM concentration) did not significantly affect either the enzyme activity or the intensity of the Ca2(+)-dependent 32P incorporation into the 140 kDa band, suggesting that the enzyme is not coupled to muscarinic binding sites.

Animals↗
PubMed1990

The role of transmembrane pH gradients in the lactic acid induced swelling of astrocytes.

The swelling of astrocytes is an important component of the morbidity and mortality associated with ischemic brain trauma. In the ischemic brain, lactic acid levels rise dramatically with a concomitant acidification of the extracellular fluid. In this study we have measured the effects of elevated extracellular lactate and reduced extracellular pH (pHo) on astrocyte volume using the human astrocyte-derived cell line UC-11MG. Neither elevated lactate nor reduced pHo alone increased cell volume, but swelling of about 25% was measured when the cells were exposed simultaneously to 20 mM lactic acid and a reduced pHo of 6. The swelling was correlated with an approximately 4-fold increase in intracellular lactate as pHo was decreased from 8.0 to 6.0. As pHo was decreased intracellular pH also decreased, but much more slowly so that at acidic extracellular pH there was an inwardly directed proton gradient. The measured intracellular lactate concentrations closely followed the theoretical levels predicted by a model in which lactate transport is coupled to the inwardly directed proton gradient. Kinetic studies indicated that lactate transport is saturable with a Km of 3.8 mM, consistent with the model for facilitated cotransport of lactate with a proton or exchange of lactate for a hydroxyl ion. These data suggest that an important mechanism of postischemic astrocytic swelling is a proton driven, active accumulation of lactate to levels that result in a significant osmotic gradient of lactate at acidic pH.

Alanine↗
PubMed1988

Arg-Lys-Asp-Val-Tyr (thymopentin) accelerates the cholinergic-induced inactivation (desensitization) of reconstituted nicotinic receptor.

1. The thymic hormone thymopoietin blocks neuromuscular transmission and was proposed (Goldstein, 1974) as a modulator of synaptic conductivity. 2. The cholinergic-induced inactivation of nicotinic receptor reconstituted into asolectin lipid vesicles was studied in the presence and in the absence of thymopentin, a synthetic pentapeptide corresponding to positions 32-36 of thymopoietin. 3. The present data show that thymopentin accelerates desensitization of the nicotinic acetylcholine receptor, supporting the aforementioned physiological role proposed for thymopoietin. 4. They also suggest that the hormone itself and/or a yet unidentified hormine-derived peptide fragment may act as an endogenous ligand for nicotinic acetylcholine receptor desensitization.

Animals↗
PubMed1988

Carbamylation of hemoglobin in vivo with chronic sublethal dietary cyanide: implications for hemoglobin S.

Carbamylation of the hemoglobin in sickle cell anemia has been demonstrated to improve the status of this hemoglobinopathy. Using an animal model of West African human patterns of chronic sublethal dietary cyanide ingestion, 12 miniature swine consuming either 0, 0.4, 0.7, or 1.2 mg of cyanide/kg body weight/day were studied for 24 weeks to determine if this dietary regime could produce irreversible carbamylated hemoglobin. Throughout the study, the hematological status of all animals remained similar; however, the levels of carbamylated hemoglobin as measured by nanomoles of valine hydantoin varied proportionally to dietary sublethal cyanide intakes, indicating that these natural dietary levels could effect an important and presumably permanent modification of the hemoglobin's beta chain. Serum thiocyanate levels were also positively correlated with cyanide ingestion loads (r = 0.83, P less than 0.01). The implications of these findings in swine are important for the millions of humans with hemoglobin S who regularly consume similar levels of dietary cyanide and for our assessments of the biochemical and medical status of hemoglobin S under natural conditions.

Animals↗
PubMed1983

The nicotinic acetylcholine receptor from Discopyge tschudii: purification, characterization and reconstitution into liposomes.

The nicotinic acetylcholine receptor from Discopyge tschudii electroplax was purified by affinity chromatography on Affi-Gel 401 using bromoacetylcholine as the ligand. Its specific activity was about 4000 pmol 125I-alpha-bungarotoxin/mg protein. SDS-polyacrylamide gel electrophoresis revealed four bands of apparent molecular weights: 41,200, 49,500, 60,000 and 66,300. The amino acid composition of each individual subunit was determined. Native membranes, rich in nicotinic receptor exhibited carbamylcholine-catalysed cation transport (blocked by curare and desensitized by prior incubation with the cholinergic agonist). The functional activity of the purified material could be reconstituted into soybean lecithin liposomes. Our data show that the Discopyge tschudii nicotinic receptor is similar to that from Torpedo californica.

Acetylcholinesterase↗
PubMedDate not supplied

[Exposure to pollutants and allergens in the asthmatic child compared with the healthy child].

To assess the frequency of exposure to allergens and indoor pollutants of school age asthmatic children at the time of their first visit to the specialist, we studied 14 cases with the diagnosis of asthma according to international criteria, and 21 healthy controls. The parents of the children filed a questionnaire asking about socio-economic level, family history of asthma, exposure to allergens or indoor pollutants, and clinical severity of the disease. Questionnaires with less than 80% of the responses were excluded from analysis. Asthmatic patients had higher frequency of exposure to tobacco smoke (42.8% vs 38%), moisture in the home walls (42.9% vs 19%), and to dust reservoirs (71.4% vs 52.4%). A high proportion of the asthmatic patients did not apply adequate environmental control measures. Education for the patients and their primary care physicians must be increased, to reduce the morbidity of the diseases.

Allergens↗