Exocytotic machinery in neuronal and endocrine tissues is sensitive to changes in intracellular Ca2+ concentration. Endocrine cell models, that are most frequently used to study the mechanisms of regulated exocytosis, are pancreatic beta cells, adrenal chromaffin cells and pituitary cells. To reliably study the Ca2+ sensitivity in endocrine cells, accurate and fast determination of Ca2+ dependence in each tested cell is required. With slow photo-release it is possible to induce ramp-like increase in intracellular Ca2+ concentration ([Ca2+]i) that leads to a robust exocytotic activity. Slow increases in the [Ca2+] i revealed exocytotic phases with different Ca2+ sensitivities that have been largely masked in step-like flash photo-release experiments. Strikingly, in the cells of the three described model endocrine tissues (beta, chromaffin and melanotroph cells), distinct Ca2+ sensitivity ‘classes’ of secretory vesicles have been observed: a highly Ca2+ -sensitive, a medium Ca2+ -sensitive and a low Ca2+ - sensitive kinetic phase of secretory vesicle exocytosis. We discuss that a physiological modulation of a cellular activity, e.g. by activating cAMP/PKA transduction pathway, can switch the secretory vesicles between Ca2+ sensitivity classes. This significantly alters late steps in the secretory release of hormones even without utilization of an additional Ca2+ sensor protein., J. Dolenšek, M. Skelin, M. S. Rupnik., and Obsahuje bibliografii a bibliografické odkazy
Experimental and epidemiological studies suggest that calcium intake is inversely related to weight gain. Calcium of dairy origin has been shown to be more effective in promoting weight loss. However, clinical studies yielded controversial results concerning the role of calcium intake in weight change. The aim of this study was to ascertain whether the addition of calcium can affect the outcome of 3-week weight management (WM) with a hypocaloric diet characterized by a decreased calcium intake. Overweight/obese women (n=67; BMI 32.2±4.1 kg/m2; age 49.1±12.1 years) underwent a 4-week comprehensive WM program. WM included a 7 MJ/day diet resulting in a stable weight during the first week and a 4.5 MJ/day diet with mean daily calcium intake 350 mg during the second to fourth week. Participants were divided into three age- and BMI-matched groups who received placebo or calcium (500 mg/day). Calcium was administered either as carbonate or calcium of dairy origin (Lactoval). There was no significant difference in weight loss in response to WM between the placebo-treated and calcium-treated groups. However, addition of calcium to the diet resulted in a lower hunger score in the Eating Inventory as well as a decrease in plasma resistin levels. Body composition measured by bioimpedance demonstrated that added calcium leads to preservation of fat-free mass. Nevertheless, a greater loss of fat-free mass in the placebo group might be partly due to a greater loss of water., K. Kabrnová-Hlavatá, V. Hainer, M. Gojová, P. Hlavatý, V. Kopský, J. Nedvídková, M. Kunešová, J. Pařízková, M. Wagenknecht, M. Hill, J. Drbohlav., and Obsahuje bibliografii a bibliografické odkazy
Previous data concerning the action of calcium (Ca) on gastric acid secretion (GAS) indicated that calcium ions increase GAS elicited by gastrin released through a vagal mechanism, and also by a direct effect on parietal cells. Our research showed that the stimulating effect of calcium on gastric acid secretion can be antagonized by verapamil administration, which reduces gastric acid secretion . In the present study we followed the effect induced by administration of calcium and Ca-chelating agents (disodium EDTA) on gastric acid secretion and on carbonic anhydrase (CA) activity. We selected two groups of healthy volunteers: Group I (n=21) received a single i.v. dose of CaCl2 (15 mg/kg b.w.), whereas Group II (n=22) received a single i.v. dose of disodium EDTA (5 mg/kg b.w.). We determined blood calcium before and after treatment, gastric acid secretion at 2 hours, erythrocyte CA II activity, and CA IV activity in membrane parietal cells, which were isolated from gastric mucosa obtained by endoscopic biopsy. Assessment of carbonic anhydrase activity was achieved by the stopped-flow method. In Group I calcium administration increased blood calcium, HCl output, CA II and CA IV activity as compared to initial values. In Group II, disodium EDTA reduced blood calcium, HCl output, CA II and CA IV activity as compared to initial values. The results demonstrated that increased blood calcium and GAS values after calcium administration correlated with the increase of erythrocyte CA II and parietal cell CA IV activity, while disodium EDTA induced a reversed process. Our results also show that cytosolic CA II and membrane CA IV values are sensitive to calcium changes and they directly depend on these levels. Our data suggest that intra- and extracellular pH changes induced by carbonic anhydrase might account for the modulation of the physiological and pathological secretory processes in the organism., I. Puscas, M. Coltau, M. Baican, G. Domuta, A. Hecht., and Obsahuje bibliografii
The rationale for the topical application of capsaicin and other vanilloids in the treatment of pain is that such compounds selectively excite and subsequently desensitize nociceptive neurons. This desensitization is triggered by the activation of vanilloid receptors (TRPV1), which leads to an elevation in intracellular free Ca2+ levels. Depending on the vanilloid concentration and duration of exposure, the Ca2+ influx via TRPV1 desensitizes the channels themselves, which may represent not only a feedback mechanism protecting the cell from toxic Ca2+ overload, but also likely contributes to the analgesic effects of capsaicin. This review summarizes the current state of knowledge concerning the mechanisms that underlie the acute capsaicin-induced Ca2+-dependent desensitization of TRPV1 channels and explores to what extent they may contribute to capsaicin-induced analgesia. In view of the polymodal nature of TRPV1, we illustrate how the channels behave in their desensitized state when activated by other stimuli such as noxious heat or depolarizing voltages. We also show that the desensitized channel can be strongly reactivated by capsaicin at concentrations higher than those previously used to desensitize it. We provide a possible explanation for a high incidence of adverse effects of topical capsaicin and point to a need for more accurate clinical criteria for employing it as a reliable remedy., L. Vyklický, K. Nováková-Toušová, J. Benedikt, A. Samad, F. Touška, V. Vlachová., and Obsahuje bibliografii a bibliografické odkazy
In the mammalian neocortex, the calcium-binding protein calretinin is expressed in a subset of cortical interneurons. In the recent years, research on interneurons is one of the most rapidly growing fields in neuroscience. This review summarizes the actual knowledge of the functions of calretinin in neuronal homeostasis and particularly of the distribution, connectivity and physiological properties of calretinin expressing interneurons in the neocortex of rodents and primates, including humans. The possible neuroprotective role of calretinin and the presumed “resistance” of calretinin-expressing interneurons to various pathological processes are also discussed., F. Barinka, R. Druga., and Obsahuje bibliografii a bibliografické odkazy
Calsequestrin is the main calcium binding protein of the sarcoplasmic reticulum, serving as an important regulator of Ca 2+ . In mammalian muscles, it exis ts as a skeletal isoform found in fast- and slow-twitch skeletal muscles and a cardiac isoform expressed in the heart and slow-twitch muscles. Recently, many excellent reviews that summarised in great detail various aspects of the calsequestrin structure, localisation or function both in skeletal and cardiac muscle have appeared. The present review focuses on skeletal muscle: information on cardiac tissue is given, where differences between both tissues are functionally important. The article reviews the known multiple roles of calsequestrin including pathology in order to introduce this topic to the broader scientific community and to stimulate an interest in this protein. Newly we describe our results on the effect of thyroid hormones on skeletal and cardiac calsequestrin expression and discuss them in the context of available literary data on this topic., P. Novák, T. Soukup., and Obsahuje bibliografii a bibliografické odkazy
Angiotensin converting enzyme (ACE) inhibition has been reported to induce regression of hypertrophy in several models of hemodynamic pressure overload. The aim of the present study was to determine whether the ACE inhibitor captopril can reduce hypertrophy of the left ventricle induced by a chronic volume overload and modify collagen composition of the hypertrophied myocardium. Rabbits with four months lasting aortic insufficiency were divided into two groups: treated with captopril (20 mg/kg/day) for five weeks and treated with placebo. The respective control groups were represented by sham-operated animals. Aortic insufficiency induced a decrease of diastolic pressure, an increase of systolic and pulse pressure, hypertrophy of the left and right ventricle, and an increase of hydroxyproline content in the left ventricle without a change of hydroxyproline concentrations in either ventricle. Captopril treatment further enhanced pulse pressure by decreasing diastolic blood pressure. Hypertrophy of the left ventricle, hydroxyproline content and concentration in both ventricles were unaffected by captopril treatment. It is concluded that ACE inhibition did not reverse the left ventricular hypertrophy developed as a result of overload induced by aortic insufficiency. We suggest that mechanisms different from activation of the renin-angiotensin system may play a decisive role in the maintenance of hypertrophy in this particular model of volume hemodynamic overload., F. Šimko, V. Pelouch, J. Kyselovic., and Obsahuje bibliografii
We studied the effects of the H2S donor Na2S on the mean arterial blood pressure (MAP) and heart and breathing rates of anesthetized Wistar rats in the presence and absence of captopril. Bolus administration of Na2S (1-4 μmol/kg) into the right jugular vein transiently decreased heart and increased breathing rates; at 8-30 μmol/kg, Na2S had a biphasic effect, transiently decreasing and increasing MAP, while transiently decreasing heart rate and increasing and decreasing breathing rate. These results may indicate independent mechanisms by which H2S influences MAP and heart and breathing rates. The effect of Na2S in decreasing MAP was less pronounced in the presence of captopril (2 μmol/l), which may indicate that the renin-angiotensin system is partially involved in the Na2S effect. Captopril decreased H2S-induced NO release from S-nitrosoglutathione, which may be related to some biological activities of H2S. These results contribute to the understanding of the effects of H2S on the cardiovascular system., M. Drobná, A. Misak, T. Holland, F. Kristek, M. Grman, L. Tomasova, A. Berenyiova, S. Cacanyiova, K. Ondrias., and Obsahuje bibliografii
The contrasting pattern of cardiac inotropy induced by human peptide endothelin-1 (ET-1) has not been satisfactorily explained. It is not clear whether ET-1 is primarily responsible for increased myocardial ET-1 expression and release with resultant inotropic effects, or for the induction of myocardial hypertrophy and heart failure. There are at least two subtypes of endothelin receptors (ETA and ETB) and the inotropic effects of ET-1 differ depending on the receptor involved. Along with some other groups, we reported significant subtype-ETB endothelin receptor down-regulation in human cardiac cells preincubated with endothelin agonists (Dřímal et al. 1999, 2000). The present study was therefore designed to clarify the subtype-selective mechanisms underlying the inotropic response to ET-1 and to its ETB-selective fragment (8-21)ET-1 in the isolated rat heart. The hearts were subjected to (1-21)ET-1 and to (8-21)ET-1, or to 30 min of stop-flow ischemia followed by 40 min of reperfusion, both before and after selective blockade of endothelin receptors.The present study revealed that both peptides, ET-1 and its (8-21)ET-1 fragment, significantly reduced coronary blood flow in nmolar and higher concentrations. The concomitant negative inotropy and chronotropy were marked after ET-1, while the infusion of the ET-1(8-21) fragment produced a slight but significant positive inotropic effect. Among the four endothelin antagonists tested in continuous infusion only the non-selective PD145065 and ETB1/B2-selective BQ788 (in mmolar concentrations) slightly reduced the early contractile dysfunction of the heart induced by ischemia, whereas ETA-selective PD155080 partially protected the rat heart on reperfusion., J. Dřímal, V. Knezl, J. Dřímal Jr , D. Dřímal, K. Bauerová , V. Kettmann, A.M. Doherty , M. Štefek., and Obsahuje bibliografii