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Cytoplasmic Ca2+ concentration changes evoked by muscarinic cholinergic stimulation in primary and metastatic melanoma cell lines.

Experiments were performed to explore differences between cultured primary and metastatic melanoma cell lines in their muscarinic acetylcholine receptor-mediated intracellular Ca signalization. The expression of type 1 and type 3 muscarinic receptors was detected and compared at the protein level using both immunocytochemistry and semiquantitative western blotting. The functionality of muscarinic receptors was tested by applying carbamylcholine (CCh; 1 mmol/l) and by recording the associated increases in cytoplasmic Ca using Ca imaging with the application of the Ca indicator dye, fluo-4. Thes

TPC2 proteins mediate nicotinic acid adenine dinucleotide phosphate (NAADP)- and agonist-evoked contractions of smooth muscle.

Agonists such as those acting at muscarinic receptors are thought to induce contraction of smooth muscle primarily through inositol 1,4,5-trisphosphate production and release of Ca(2+) from sarcoplasmic reticulum. However, the additional Ca(2+)-mobilizing messengers cyclic adenosine diphosphate ribose (cADPR) and nicotinic acid adenine dinucleotide phosphate (NAADP) may also be involved in this process, the former acting on the sarcoplasmic reticulum, the latter acting on lysosome-related organelles. In this study, we provide the first systematic analysis of the capacity of inositol 1,4,5-tris

Juvenile pig detrusor: effects of propiverine and three of its metabolites.

In isolated detrusor strips, propiverine is known to be effective to decrease contractions elicited by electric field stimulation (EFS). Here we investigated whether the metabolites M-5, M-6 and M-14 of propiverine retain the pharmacological properties of the parent compound also in juvenile organisms. EFS-induced contractions of detrusor strips from juvenile pigs are more sensitive to atropine than strips from mature pigs. The atropine-resistant component of contraction is also significantly larger in juvenile pigs. Propiverine, its metabolites M-5, M-14 and also tolterodine completely reduce

Nonselective cation channels activated by the stimulation of muscarinic receptors in mammalian gastric smooth muscle.

Muscarinic receptors play key roles in the control of gastrointestinal smooth muscle activity. However, specific physiological functions of each subtype remain to be determined. Single cell RT-PCR experiments showed that all five subtypes of muscarinic receptors were present in circular smooth muscle cells of the guinea-pig gastric antrum. Nonselective cation channels (NSCC) activated by ACh or CCh are coupled to pertussis toxin (PTX)-sensitive Go protein through m4 subtype as well as m2 and m3 subtypes in guinea-pig stomach. CCh-activated currents (I(CCh)), especially the steady-state I-V rel

Correlation of EGTA and calcium-blocking agents on the response of the bladder to in vitro ischemia.

Loss-of-function mutations in genes encoding the Krebs cycle enzymes Fumarate Hydratase (FH) and Succinate Dehydrogenase (SDH) induce accumulation of fumarate and succinate, respectively and predispose patients to hereditary cancer syndromes including the development of aggressive renal cell carcinoma (RCC). Fumarate and succinate competitively inhibit αKG-dependent dioxygenases, including Lysine-specific demethylase 4A/B (KDM4A/B), leading to suppression of the homologous recombination (HR) DNA repair pathway. In this study, we have developed new syngeneic Fh1- and Sdhb-deficient murine model

Site-directed mutagenesis of the m3 muscarinic receptor: identification of a series of threonine and tyrosine residues involved in agonist but not antagonist binding.

The hydrophobic core of all muscarinic receptors contains several conserved serine, threonine and tyrosine residues, most of which do not occur in any other G-protein coupled receptor. Since these amino acids can serve as potential hydrogen bond donors or acceptors, we have tested the hypothesis that they may be involved in the selective binding of muscarinic ligands. To eliminate the OH groups present in these residues, we have created nine single point mutations in the rat m3 muscarinic receptor by converting serine and threonine residues to alanine, and tyrosine residues to phenylalanine. T

Studies of isolated parietal and enterochromaffin-like cells from the rat.

Rat gastric mucosal cells isolated by enzyme dispersion were separated by elutriation centrifugation. The amount of histamine and the number … . Scattered ECL cells were also present in the fraction enriched with parietal cells. Histamine and carbacholine stimulated aminopyrine uptake in a concentration-dependent manner with about the same efficacy, 5.6 times the base-line value. When combined with the phosphodiesterase inhibitor isobutyl methylxanthine, the maximal histamine stimulation was incre …

Regulation of phosphatidylinositol turnover in brain synaptoneurosomes: stimulatory effects of agents that enhance influx of sodium ions.

Norepinephrine and carbamoylcholine stimulate accumulation of [3H]inositol phosphates from [3H]inositol-labeled guinea pig cerebral cortical synaptoneurosomes through interaction with alpha 1-adrenergic and muscarinic receptors, respectively. In addition to such agonist, a variety of natural products that affect voltage-dependent sodium channels can markedly stimulate accumulation of [3H]inositol phosphates. These include alkaloids that activate sodium channels, such as batrachotoxin, veratridine, and aconitine; peptide toxins that alter activation or slow inactivation of sodium channels, such

The influence of antibiotics on agonist occupation and functional states of the nicotinic acetylcholine receptor.

Four distinct classes of antibiotics, the aminoglycosides, tetracyclines, lincomycin-clindamycin, and peptides, were examined in intact BC3H-1 cells for their capacity to influence the relationship between agonist binding to the cholinergic receptor and the response elicited. The most potent inhibitors were the peptides of the polymyxin-colistin class, which at submicromolar concentrations noncompetitively blocked agonist-elicited Na+ permeability. These agents at equivalent concentrations also enhanced the apparent affinity of agonists for the receptor. Comparisons of agonist occupation of th

Osteoporosis risk in patients with primary open-angle glaucoma using muscarinic and prostaglandin agonists: A retrospective cohort study.

BackgroundGlaucoma is the leading cause of irreversible blindness worldwide, with primary open-angle glaucoma (POAG) arising as the most com … ravoprost, tafluprost) without muscarinic agonist use, or muscarinic M3 agonists (e.g. pilocarpine, carbachol) without prostaglandin analog use. Propensity score matching was performed for age, sex, comorbidities, and concurrent glaucoma medications to limit possible cofounders. The outcome was defined as a diagnosis of osteoporosis without current patholog …

Cryptotanshinone as a Multi-Target Natural Terpenoid with Bronchodilator Potential: Insights from Integrated In Vitro and In Silico Studies.

Asthma is a chronic airway disease characterized by inflammation, bronchial hyperresponsiveness, and airflow limitation, highlighting the ne … eal smooth muscle preparations. The relaxant effects of CT (10-7-3 × 10-4 M) were evaluated against carbachol (1 µM)- and high-K+ (80 mM)-induced contractions. Docking predicted favorable binding of CT to the M3 receptor and L-type Ca2+ channel, with binding energies of -9.854 and -9.951 kcal/mol, respectively. In vitro, CT produced concentration-dependent …

Evaluation of pharmacokinetics, pharmacodynamics, and toxicity of potential quinazoline bronchodilators derived from vasicinone.

Various synthetic modifications of the alkaloid (-)-vasicinone are known to exhibit a remarkable bronchodilatory effect. This study aimed to … affinity (pKB higher than pKI for M1 and M3 receptors, P < .05) and exert functional antagonism of carbachol-induced response. The main effect is not accompanied by a concomitant antibiotic effect. The proven inhibition of muscarinic receptors including the M3 subtype is analogous to the effects of clinically used anticholinergic bronchodilators. Therefore …

ДиметилФумарат Аттенуаты циклофосфамидозные повреждения мочевого пузыря и усиление цитотоксичной активности против клеток SH-SY5Y.

Острый кистит, вызванный циститом цилофосфамида (КХ), является изнурительной дисфункцией мочевого пузыря, которая, как правило, наблюдается у больных раком, главным образом в результате окислительных повреждений и воспаления тканей мочевого пузыря. Диметилфумарат (DMF) — эстер фумарной кислоты, утвержденный для лечения множественных склерозов в силу его антиоксидантов и противовоспалительных свойств. Таким образом, мы намеревались изучить многообразное воздействие ДМФ, включая как его потенциальное синергетическое воздействие с ХП на клетки SH-SY5Y, так и его незащищенное воздействие на острый

Совпадение в аннотации оригинала
Cylophosphamide (CP)-induced acute cystitis is a debilitating bladder dysfunction commonly observed in cancer patients, primarily resulting … esical vascular permeability. SH-SY5Y cell viability was assayed by MTT test. CP markedly decreased carbachol-induced contraction of detrusor strips (p < 0.01), which was prevented by the high-dose DMF treatment (p < 0.05). Evans blue dye extravasation was greatly increased in the bladders of cystitis group (p < 0.001), which was significantly decreased in …

Pharmacological Validation for the Folklore Use of Ipomoea nil against Asthma: In Vivo and In Vitro Evaluation.

Oxidative stress is the key factor that strengthens free radical generation which stimulates lung inflammation. The aim was to explore antio … gavage of In.Cr at different doses in rabbits showed a better brochodilation profile as compared to carbachol and K+-induced bronchospasm. More significant (p < 0.01) reduction in OVA-induced allergic hyper-responses i.e., inflammatory cells grade, antibody IgE as well as altered IFN-α in airways were observed at three different doses of In.Cr. It can be co …

The Spasmolytic, Bronchodilator, and Vasodilator Activities of Parmotrema perlatum Are Explained by Anti-Muscarinic and Calcium Antagonistic Mechanisms.

Parmotremaperlatum is traditionally used in different areas of Pakistan to treat gastrointestinal, respiratory, and vascular diseases. This study evaluates the underlying mechanisms for traditional uses of P. perlatum in diarrhea, asthma, and hypertension. In vitro pharmacological studies were conducted using isolated jejunum, trachea, and aortic preparations, while the cytotoxic study was conducted in mice. Crude extract of P. perlatum(Pp.Cr), comprising appreciable quantities of alkaloids and flavonoids, relaxed spontaneously contracting jejunum preparation, K+ (80 mM)-induced, and carbachol…

Pharmacological Studies Pertaining to Smooth Muscle Relaxant, Platelet Aggregation Inhibitory and Hypotensive Effects of Ailanthus altissima.

OBJECTIVE: This in vitro and in vivo study was conducted to rationalize some of traditional medicinal uses of Ailanthus altissima in gastroi … o observed. Relaxant effect was observed by the application of Aa.Cr and Aa.DCM against high-K+ and carbachol (CCh) induced contractions in tracheal strips isolated from SD rats, while Aa.Aq caused partial relaxation of high-K+ induced contractions, but no effect was observed against CCh induced contractions. Relaxation of rat aorta by the application of Aa …

Resolvin D2 elevates cAMP to increase intracellular [Ca2+] and stimulate secretion from conjunctival goblet cells.

Under physiologic conditions, conjunctival goblet cells (CGCs) secrete mucins into the tear film to preserve ocular surface homeostasis. Spe … MP inhibited the increase in [Ca2+]i stimulated by the cAMP-independent agonist cholinergic agonist carbachol. In conclusion, RvD2 uses both cellular cAMP and [Ca2+]i to stimulate glycoconjugate secretion from CGCs, but the interaction of cAMP and [Ca2+]i is context dependent. Thus RvD2 likely assists in the maintenance of the mucous layer of the tear film …