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Adv Exp Med Biol ; 1131: 163-182, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31646510


Calcium (Ca2+) buffering is part of an integrative crosstalk between different mechanisms and elements involved in the control of free Ca2+ ions persistence in the cytoplasm and hence, in the Ca2+-dependence of many intracellular processes. Alterations of Ca2+ homeostasis and signaling from systemic to subcellular levels also play a pivotal role in the pathogenesis of many diseases.Compared with Ca2+ sequestration towards intracellular Ca2+ stores, Ca2+ buffering is a rapid process occurring in a subsecond scale. Any molecule (or binding site) with the ability to bind Ca2+ ions could be considered, at least in principle, as a buffer. However, the term Ca2+ buffer is applied only to a small subset of Ca2+ binding proteins containing acidic side-chain residues.Ca2+ buffering in the cytoplasm mainly relies on mobile and immobile or fixed buffers controlling the diffusion of free Ca2+ ions inside the cytosol both temporally and spatially. Mobility of buffers depends on their molecular weight, but other parameters as their concentration, affinity for Ca2+ or Ca2+ binding and dissociation kinetics next to their diffusional mobility also contribute to make Ca2+ signaling one of the most complex signaling activities of the cell.The crosstalk between all the elements involved in the intracellular Ca2+ dynamics is a process of extreme complexity due to the diversity of structural and molecular elements involved but permit a highly regulated spatiotemporal control of the signal mediated by Ca2+ ions. The basis of modeling tools to study Ca2+ dynamics are also presented.

Sinalização do Cálcio , Cálcio , Citoplasma , Animais , Tampões (Química) , Cálcio/metabolismo , Sinalização do Cálcio/fisiologia , Citoplasma/metabolismo , Humanos
Am J Vet Res ; 80(2): 201-207, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30681357


OBJECTIVE To determine the pharmacokinetics of meloxicam in African grey parrots (Psittacus erithacus) during administration of multiple doses. ANIMALS 6 healthy African grey parrots. PROCEDURES Meloxicam was administered at each of 3 dosages (1 mg/kg, IM, q 24 h, for 7 days; 1 mg/kg, PO, q 24 h, for 12 days; and 1.6 mg/kg, PO, q 24 h, for 7 days) with an 8-week washout period between treatments. Blood samples were collected 12 and 24 hours after each drug administration (times of presumptive peak and trough drug concentrations) for pharmacokinetic analysis. Birds were visually assessed during all experiments and monitored for changes in selected plasma and urine biochemical variables after administration of the drug at 1.6 mg/kg. RESULTS Mean trough plasma concentrations at steady state were 10.7 and 9.16 µg/mL after meloxicam administration at 1 mg/kg, IM, and 1 mg/kg, PO, respectively. Plasma drug accumulation was evident (accumulation ratios of 2.04 ± 0.30 [IM treatment] and 2.45 ± 0.26 [PO treatment]). Plasma and urine N-acetyl-ß-d-glucosaminidase activities were significantly increased at the end of meloxicam treatment at 1.6 mg/kg. CONCLUSIONS AND CLINICAL RELEVANCE Plasma concentrations of meloxicam were maintained at values greater than effective analgesic concentrations described for other avian species. Although administration of meloxicam at a dosage of 1 mg/kg IM and PO daily for 1 week and 12 days, respectively, was not associated with adverse clinical effects in this population, further studies are needed to assess the efficacy and safety of the drug during prolonged treatment and the clinical relevance of its accumulation.

Anti-Inflamatórios não Esteroides/farmacocinética , Meloxicam/farmacocinética , Papagaios/sangue , Administração Oral , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Esquema de Medicação , Meia-Vida , Injeções Intramusculares , Meloxicam/administração & dosagem
Adv Exp Med Biol ; 740: 483-98, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22453955


Calcium buffering is one of the mechanisms to control calcium (Ca(2+)) persistence in the cytosol and hence, Ca(2+) dependence of many intracellular processes. Compared with Ca(2+) sequestration into intracellular Ca(2+) stores, Ca(2+) buffering is a rapid process occurring in sub-second scale.Ca(2+) buffers can be mobile or fixed depending of their molecular weight, but other parameters as their concentration, affinity for Ca(2+) or Ca(2+) binding and releasing kinetics are important to know their role in Ca(2+) signaling.This process determines Ca(2+) diffusion and spatiotemporal Ca(2+) signaling in the cell and is one of the basis of the versatility and complexity of Ca(2+) as intracellular messenger.

Cálcio/metabolismo , Citoplasma/metabolismo , Animais , Tampões (Química) , Sinalização do Cálcio , Humanos
J Biol Chem ; 281(47): 35616-23, 2006 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-16982621


A sustained Ca2+ entry is the primary signal for T lymphocyte activation after antigen recognition. This Ca2+ entry mainly occurs through store-operated Ca2+ channels responsible for a highly selective Ca2+ current known as I(CRAC). Ca2+ ions act as negative feedback regulators of I(CRAC), promoting its inactivation. Mitochondria, which act as intracellular Ca2+ buffers, have been proposed to control all stages of CRAC current and, hence, intracellular Ca2+ signaling in several types of non-excitable cells. Using the whole-cell configuration of the patch clamp technique, which allows control of the intracellular environment, we report here that respiring mitochondria located close to CRAC channels can regulate slow Ca2+-dependent inactivation of I(CRAC) by increasing the Ca2+-buffering capacity beneath the plasma membrane, mainly through the release of ATP.

Trifosfato de Adenosina/química , Cálcio/metabolismo , Proteínas de Membrana/química , Mitocôndrias/metabolismo , Cálcio/química , Canais de Cálcio/metabolismo , Membrana Celular/metabolismo , Quelantes/farmacologia , Eletrofisiologia , Citometria de Fluxo , Humanos , Membranas Intracelulares/metabolismo , Células Jurkat , Proteína ORAI1 , Técnicas de Patch-Clamp , Transdução de Sinais