Homocysteine is increasingly recognized as an important molecule in a wide variety of cellular functions [...
View Article and Find Full Text PDFHomocysteine is a sulfur-containing endogenous amino acid leading to neurotoxic effects at high concentrations. Population studies suggest an association between plasma homocysteine levels and the risk of migraine headaches. The aim of this study was to analyze the sensitivity of rats with prenatal hyperhomocysteinemia (hHCY) in respect of the development of behavioral correlates of headache and spreading cortical depolarization (CSD) in a migraine model induced by the administration of the nitric oxide (NO) donor nitroglycerin.
View Article and Find Full Text PDFHomocysteine is a non-proteinogenic sulfhydryl-containing amino acid derived from methionine and is a homologue of cysteine [...
View Article and Find Full Text PDFPflugers Arch
January 2021
Acetaldehyde and acetic acid/acetate, the active metabolites of alcohol (ethanol, EtOH), generate actions of their own ranging from behavioral, physiological, to pathological/cancerogenic effects. EtOH and acetaldehyde have been studied to some depth, whereas the effects of acetic acid have been less well explored. In this study, we investigated the effect of acetic acid on big conductance calcium-activated potassium (BK) channels present in GH3 rat pituitary tumor cells in more detail.
View Article and Find Full Text PDFHydrogen sulfide (HS) is endogenously produced from sulfur containing amino acids, including homocysteine and exerts neuroprotective effects. An increase of homocysteine during pregnancy impairs fetal growth and development of the offspring due to severe oxidative stress. We analyzed the effects of the HS donor-sodium hydrosulfide (NaHS) administered to female rats with hyperhomocysteinemia (hHcy) on behavioral impairments and levels of oxidative stress of their offspring.
View Article and Find Full Text PDFBackground: Tuberculosis (TB) is the second important cause of death worldwide caused by a bacterium called . There is a need to find and develop new Anti-TB medications that are effective, inexpensive and suitable with human immunodeficiency virus and other anti-TB drugs used in many countries and mainly the developing countries where the disease is widespread. These drugs must be designed to shorten treatment time and to be active against resistant forms of the mycobacteria that will help to increase the patients compliance.
View Article and Find Full Text PDFHydrogen sulfide (HS), a well-established member of the gasotransmitter family, is involved in a variety of physiological functions, including pro-nociceptive action in the sensory system. Although several reports have shown that HS activates sensory neurons, the molecular targets of HS action in trigeminal (TG) nociception, implicated in migraine, remains controversial. In this study, using suction electrode recordings, we investigate the effect of the HS donor, sodium hydrosulfide (NaHS), on nociceptive firing in rat meningeal TG nerve fibers.
View Article and Find Full Text PDFIn this study, we investigated the effects of L-homocysteine (Hcy) on maxi calcium-activated potassium (BK) channels and on exocytosis of secretory granules in GH3 rat pituitary-derived cells. A major finding of our study indicates that short-term application of Hcy increased the open probability of oxidized BK channels in inside-out recordings. Whole-cell recordings show that extracellular Hcy also augmented BK currents during long-term application.
View Article and Find Full Text PDFThe aim of the present study was to evaluate the effects of hydrogen sulfide (H2S) on the membrane potential, action potential discharge and exocytosis of secretory granules in neurosecretory pituitary tumor cells (GH3). The H2S donor - sodium hydrosulfide (NaHS) induced membrane hyperpolarization, followed by truncation of spontaneous electrical activity and decrease of the membrane resistance. The NaHS effect was dose-dependent with an EC50 of 152 μM (equals effective H2S of 16-19 μM).
View Article and Find Full Text PDFAll cells contain ion channels in their outer (plasma) and inner (organelle) membranes. Ion channels, similar to other proteins, are targets of oxidative impact, which modulates ion fluxes across membranes. Subsequently, these ion currents affect electrical excitability, such as action potential discharge (in neurons, muscle, and receptor cells), alteration of the membrane resting potential, synaptic transmission, hormone secretion, muscle contraction or coordination of the cell cycle.
View Article and Find Full Text PDFIntroduction: Gases, such as nitric oxide (NO), carbon monoxide (CO), or hydrogen sulfide (H2S), termed gasotransmitters, play an increasingly important role in understanding of how electrical signaling of cells is modulated. H2S is well-known to act on various ion channels and receptors. In a previous study we reported that H2S increased calcium-activated potassium (BK) channel activity.
View Article and Find Full Text PDFPolyamines, which are obligatory molecules involved in cell cycling and proliferation, are subject to a change in their free intracellular concentrations during the cell cycle. Potassium (K(+)) channels are also considered, but less well recognized, to be necessary for cell proliferation by either hyperpolarizing or depolarizing cells during the cell cycle. A block of polyamine synthesis as well as block or knockout of K(+) channels can halt cell proliferation.
View Article and Find Full Text PDFBackground: In the central nervous system ethanol (EtOH) is metabolized to acetaldehyde (ACA) primarily by the oxidative enzyme catalase. Evidence suggests that ACA is responsible for at least some of the effects on the brain that have been attributed to EtOH. Various types of ion channels which are involved in electrical signaling are targets of EtOH like maxi calcium-activated potassium (BK) channels.
View Article and Find Full Text PDFNaunyn Schmiedebergs Arch Pharmacol
September 2013
A series of sulfanilamide Schiff base derivatives (1 to 15) have been designed as potential antitubulin agents depending on the chemical structures of combretastatine A-4 and isoquinoline sulfamate (antimitotic agents under investigation). The designed compounds were synthesized by microwave chemical synthesis, their purity was confirmed by melting point and HPLC and chemical structures were determined by FT-IR, UV, and 1H and 13C-NMR spectroscopic techniques. The synthesized compounds have been docked in the colchicine binding site of β-tubulin using molecular modeling programs and the antitumor activities were screened on human breast and lung cancer cells by cell counting assay.
View Article and Find Full Text PDFS100 Ca(2+)-binding proteins have been associated with a multitude of intracellular Ca(2+)-dependent functions including regulation of the cell cycle, cell differentiation, cell motility and apoptosis, modulation of membrane-cytoskeletal interactions, transduction of intracellular Ca(2+) signals, and in mediating learning and memory. S100 proteins are fine tuned to read the intracellular free Ca(2+) concentration and affect protein phosphorylation, which makes them candidates to modulate certain ion channels and neuronal electrical behavior. Certain S100s are secreted from cells and are found in extracellular fluids where they exert unique extracellular functions.
View Article and Find Full Text PDFHydrogen sulfide (H(2)S) is the third gasotransmitter found to be produced endogenously in living cells to exert physiological functions. Large conductance (maxi) calcium-activated potassium channels (BK), which play an important role in the regulation of electrical activity in many cells, are targets of gasotransmitters. We examined the modulating action of H(2)S on BK channels from rat GH(3) pituitary tumor cells using patch clamp techniques.
View Article and Find Full Text PDFProteinase-activated receptor 2 (PAR-2) has been shown to elicit secretion in a variety of secretory epithelial cells by the transepithelial movement of chloride ions across the apical membrane. However, it is not known whether these receptors are present and/or functional in the secretory epithelial cells of the human eccrine sweat gland. To investigate this possibility mRNA analysis, Ca2+ microspectrofluorimetry and the short circuit current (Isc) technique were used to quantify electrolyte transport in a cell line (NCL-SG3) derived from human eccrine sweat gland secretory epithelia.
View Article and Find Full Text PDFBackground: Padma Lax (PL) is a multi-component herbal laxative, derived from traditional Tibetan medicine. It has been used in the treatment of constipation dominant irritable bowel syndrome. Beyond its purgative and bowel-regulating properties we found it to exhibit antiproliferative properties.
View Article and Find Full Text PDFThe hypothalamic galanin-like peptide (GALP) was isolated by its ability to activate galanin receptors. The mature porcine GALP is a 60-amino acid neuropeptide proteolytically processed from a 120-amino acid precursor protein. It contains a region identical to the N-terminal 13-amino acids of the neuropeptide galanin.
View Article and Find Full Text PDFWe studied the impact of an NO-cGMP dependent signalling pathway on the high-voltage-activated (HVA) Ca(2+) current in identified neurons of the pulmonate snail, Helix pomatia, using Ba(2+) as charge carrier. The 3',5'-cyclic guanosine monophosphate (cGMP) analogues, dibutyryl-cGMP and 8-bromo-cGMP, consistently induced a biphasic response, consisting of an increase superseded by a decline of the Ba(2+) current. The NO donor, sodium nitroprusside (SNP), modulated only in a minority of neurons the Ba(2+) current.
View Article and Find Full Text PDFWe present a first description of annexin immunoreactivity within the teleost retina. Antibodies against annexins V and VI were used in light and electron microscopic sections of light- and dark-adapted retinae. Strong immunoreactivity could be found in retinal layers with high synaptic input, such as the outer and inner plexiform layers and dendritic regions within the inner plexiform layer, in cells that are involved in negative feedback control such as horizontal and amacrine cells, in the membrane metabolism of photoreceptor outer segments, and in close relation to cytoskeletal components.
View Article and Find Full Text PDFIn the present study, we investigated the underlaying mechanism of nitric oxide (NO) and cGMP on the decline of a Ca2+-activated potassium (KCa) current in U-cells of the right parietal ganglion of the pulmonate snail, Helix pomatia. Using a two-electrode voltage-clamp technique, we activated a KCa-current either by opening of endogenous voltage-gated Ca2+-channels during depolarizing voltage steps or by ionophoretic injection of Ca2+ via a third electrode containing 100 mM Ca2+. KCa-current amplitude in U-cells was sensitive to Ba2+, TEA, iberiotoxin, kaliotoxin and charybdotoxin (ChTX), but not to 4-aminopyridine (4-AP) (up to 30 mM) and apamin (up to 300 nM).
View Article and Find Full Text PDFRecently we have shown that galanin binding significantly correlates with survival in neuroblastoma patients, indicating a possible modulatory role of galanin receptors in neuroblastic tumor biology. However, the molecular mechanisms beyond this correlation have not been elucidated. Here, the cellular effects on activation of specific galanin receptor subtypes in human SH-SY5Y neuroblastoma cells were analyzed using a tetracycline-controlled expression system.
View Article and Find Full Text PDFSeasonal variations can be found in almost any parameter of an organism's biochemistry, physiology, endocrinology, and behaviour. This phenomenon, generally called photoperiodism, results from one of the major functions of the circadian system, i.e.
View Article and Find Full Text PDF