Biomedical subjects

A Tepikin

Publications and source records attributed to A Tepikin.

5 recordsLinked to original sources

PubMed2005

Free radicals and the pancreatic acinar cells: role in physiology and pathology.

Reactive oxygen and nitrogen species (ROS and RNS) play an important role in signal transduction and cell injury processes. Nitric oxide synthase (NOS)-the key enzyme producing nitric oxide (NO)-is found in neuronal structures, vascular endothelium and, possibly, in acinar and ductal epithelial cells in the pancreas. NO is known to regulate cell homeostasis, and its effects on the acinar cells are reviewed here. ROS are implicated in the early events within the acinar cells, leading to the development of acute pancreatitis. The available data on ROS/RNS involvement in the apoptotic and necrotic death of pancreatic acinar cells will be discussed.

Apoptosis↗

PubMed2003

Calcium signalling in and around the nuclear envelope.

We have compared calcium mobilization by Ins(1,4,5) P(3)(IP(3)), cADP-ribose (cADPR) and nicotinic acid-adenosine dinucleotide phosphate (NAADP) from the envelope of isolated nuclei with the calcium signalling in intact isolated pancreatic acinar cells. Ca(2+) uptake and release were studied with calcium-sensitive fluorescent probes. In the present study, we have shown that all calcium messengers induce Ca(2+) release from the nuclear envelope. Pre-treatment of nuclei with thapsigargin completely abolished the responses to the calcium messengers, indicating that Ca(2+) stores in isolated nuclei are thapsigargin-sensitive. Using different pharmacological tools, we show that Ca(2+) release from pancreatic nuclei is unlikely to occur from stores other than those with endoplasmic reticulum characteristics. We conclude that all three calcium messengers can release Ca(2+) from pancreatic acinar nuclear stores, as previously shown for IP(3) and cADPR. It would appear that NAADP releases Ca(2+) from the same IP(3)- and cADPR-sensitive stores with endoplasmic reticulum characteristics.

Animals↗

PubMed2002

Correlation of NADH and Ca2+ signals in mouse pancreatic acinar cells.

Relationships between calcium signals and NADH responses were investigated in pancreatic acinar cells stimulated with calcium-releasing secretagogues. Cytosolic calcium signals were studied using Fura Red or calcium-sensitive Cl(-) current. Mitochondrial calcium was measured using Rhod-2. The highest levels of NADH autofluorescence were found around the secretory granule region. Stimulation of cells with physiological doses of cholecystokinin (CCK) triggered slow oscillations of NADH autofluorescence. NADH oscillations were clearly resolved in the mitochondrial clusters around secretory granules. Very fast apical calcium signals induced by acetylcholine (ACh) produced no detectable changes in NADH; slightly more extended apical (or preferentially apical) calcium transients triggered clear NADH responses. Triple combined recordings of cytosolic calcium, mitochondrial calcium and NADH revealed the sequence of development of individual signals: an increase in cytosolic calcium was accompanied by a slower mitochondrial calcium response followed by a delayed increase in NADH fluorescence. Recovery of cytosolic calcium was faster than recovery of mitochondrial calcium. NADH recovery occurred at elevated mitochondrial calcium levels. During the transient cytosolic calcium oscillations induced by intermediate doses of ACh, there was an initial increase in NADH fluorescence following the first calcium transient; each of the subsequent calcium responses produced biphasic NADH changes comprising an initial small decline followed by restoration to an elevated calcium level. During the higher-frequency sinusoidal calcium oscillations induced by higher doses of ACh, NADH responses fused into a smooth rise followed by a slow decline. Supramaximal doses of ACh and CCK produced single large NADH transients.

Acetylcholine↗

PubMed2001

The endoplasmic reticulum: one continuous or several separate Ca(2+) stores?

The Ca2+ store and sink in the endoplasmic reticulum (ER) is important for Ca2+ signal integration and for conveyance of information in spatial and temporal domains. Textbooks regard the ER as one continuous network, but biochemical and biophysical studies revealed apparently discrete ER Ca2+ stores. Recent direct studies of ER lumenal Ca2+ movements show that this organelle system is one continuous Ca2+ store, which can function as a Ca2+ tunnel. The concept of a fully connected ER network is entirely compatible with evidence indicating that the distribution of Ca2+ -release channels in the ER membrane is discontinuous with clustering in certain localities.

Calcium↗

PubMed1993

Calcium clamp in isolated neurones of the snail Helix pomatia.

1. Intracellular free calcium concentration ([Ca2+]i) in isolated non-identified Helix pomatia neurones has been clamped at different physiologically significant levels by a feedback system between the fluorescent signal of fura-2 probe loaded into the cell and ionophoretic injection of Ca2+ ions through a CaCl2-loaded microelectrode. The membrane potential of the neurone has also been clamped using a conventional two-microelectrode method. 2. Special measurements have shown that the transport indices of injecting microelectrodes filled with 50 mM CaCl2 are quite variable (0.11 +/- 0.06, mean +/- S.D.). However, for each electrode the transport indices remained stable during several injection trials into a solution drop having the size of a neurone. The spread of calcium ions from the tip of the microelectrode across the cytosol of the neurone terminated within 2-4 s. The spatial difference in [Ca2+]i at this time did not exceed 10%. 3. Clamping of [Ca2+]i at a new increased level was accompanied by a transient of the Ca(2+)-injecting current. To increase [Ca2+]i by 0.1 microM, the amount of calcium ions injected during this stage had to be 36 +/- 20 microM Ca2+ per cell volume. Obviously, this transient represents the filling of a fast cytosolic buffer which has to be saturated to reach a new increased level of [Ca2+]i. It was followed by a steady component of Ca(2+)-injecting current, which was quite low (corresponding to injection of 0.39 +/- 0.20 microM s-1 for a 0.1 microM change of [Ca2+]i). This may represent the functioning of Ca(2+)-eliminating systems and corresponds to a similar amount of Ca2+ extruded from the cytoplasm. 4. Changes in the injection current also developed when Ca2+ influx through the membrane was triggered by the activation of voltage-gated calcium channels. The amount of Ca2+ entering the cell during the first seconds of depolarization to--15 mV was equal to 0.59 +/- 0.31 microM s-1 per cell volume. 5. No activation of Ca(2+)-dependent potassium current was observed during the changes in [Ca2+]i to levels exceeding the basal one by several times. Obviously, to activate this current, a much stronger increase in [Ca2+]i is needed in the immediate vicinity of the corresponding channels.

Animals↗