Role of acetylcholine and calcium ions in three vascular contraction models: Angiotensin II, phenylephrine and caffeine

Szadujkis-Szadurska, Katarzyna; Grześk, Grzegorz; Szadujkis-Szadurski, Leszek; Gajdus, Marta; Matusiak, Grzegorz

doi:10.3892/etm.2012.573

Cited by 9 publications

(10 citation statements)

References 20 publications

(20 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Non-competitive inhibitors blocking anionic sites of AChE are known to be able to improve cognitive functions during Alzheimer disease [5,18,38], and caffeine would act just as the non-competitive inhibitor. Besides the improving cognitive functions, there are hypotheses that the blocking of the peripheral anionic site of AChE could slow down deposition of amyloid plaques [4,5].…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Caffeine Inhibits Acetylcholinesterase, But Not Butyrylcholinesterase

Pohanka

Dobeš

2013

IJMS

View full text Add to dashboard Cite

Caffeine is an alkaloid with a stimulant effect in the body. It can interfere in transmissions based on acetylcholine, epinephrine, norepinephrine, serotonin, dopamine and glutamate. Clinical studies indicate that it can be involved in the slowing of Alzheimer disease pathology and some other effects. The effects are not well understood. In the present work, we focused on the question whether caffeine can inhibit acetylcholinesterase (AChE) and/or, butyrylcholinesterase (BChE), the two enzymes participating in cholinergic neurotransmission. A standard Ellman test with human AChE and BChE was done for altering concentrations of caffeine. The test was supported by an in silico examination as well. Donepezil and tacrine were used as standards. In compliance with Dixon’s plot, caffeine was proved to be a non-competitive inhibitor of AChE and BChE. However, inhibition of BChE was quite weak, as the inhibition constant, Ki, was 13.9 ± 7.4 mol/L. Inhibition of AChE was more relevant, as Ki was found to be 175 ± 9 μmol/L. The predicted free energy of binding was −6.7 kcal/mol. The proposed binding orientation of caffeine can interact with Trp86, and it can be stabilize by Tyr337 in comparison to the smaller Ala328 in the case of human BChE; thus, it can explain the lower binding affinity of caffeine for BChE with reference to AChE. The biological relevance of the findings is discussed.

show abstract

Section: Resultsmentioning

confidence: 99%

“…However, the adenosine receptors are not the only targets of caffeine. It can meet acetylcholine-, epinephrine-, norepinephrine-, serotonin-, dopamine- and glutamate-mediated neurotransmission [18–22]. Phosphodiesterases inhibition and promotion of calcium release from intracellular stores can be attributed to caffeine, as well [23,24].…”

Section: Introductionmentioning

confidence: 99%

Caffeine Inhibits Acetylcholinesterase, But Not Butyrylcholinesterase

Pohanka

Dobeš

2013

IJMS

View full text Add to dashboard Cite

show abstract

“…Caffeine has been known for its use as a stimulant supplement which is based on nonselective adenosine receptor antagonism . Additional targets include acetylcholine‐, epinephrine‐, norepinephrine‐, serotonin‐, dopamine‐, and glutamate‐mediated neurotransmission . Caffeic acid (3,4‐dihydroxycinnamic acid) is a phenolic (nonflavonoid) catecholic compound abundantly present in almost all plants and dietary substances …”

Section: Caffeine and Caffeic Acidmentioning

confidence: 99%

Cholinesterase targeting by polyphenols: A therapeutic approach for the treatment of Alzheimer’s disease

2018

View full text Add to dashboard Cite

Alzheimer's disease (AD) is a progressive irreversible neurodegenerative disorder characterized by excessive deposition of β-amyloid (Aβ) oligomers, and neurofibrillary tangles (NFTs), comprising of hyperphosphorylated tau proteins. The cholinergic system has been suggested as the earliest and most affected molecular mechanism that describes AD pathophysiology. Moreover, cholinesterase inhibitors (ChEIs) are the potential class of drugs that can amplify cholinergic activity to improve cognition and global performance and reduce psychiatric and behavioral disturbances. Approximately, 60%-80% of all cases of dementia in the world are patients with AD. In view of the continuous rise of this disease especially in the aged population, there is a dire need to come up with a novel compound and/or mixture that could work against this devastating disease. In this regard, the best is to rely on natural compounds rather than synthetic ones, because natural compounds are easily available, cost-effective, and comparatively less toxic. To serve this purpose, lately, scientific community has started exploring the possibility of using different polyphenols either solitary or in combination that can serve as therapeutics against AD. In the current article, we have summarized the role of various polyphenols, namely quercetin, resveratrol, curcumin, gallocatechins, cinnamic acid, caffeine, and caffeic acid as an inhibitor of cholinesterase for the treatment of AD. We have also tried to uncover the mechanistic insight on the action of these polyphenols against AD pathogenicity.

show abstract

“…The results of the present study performed using the second experimental model indicate a balanced increase in calcium influx from an intracellular and extracellular calcium pool, suggesting a particular pathway activation at a stage no later than phospholipase C. Activation of the calcium influx following stimulation of the ryanodine receptor induces a calcium influx from the intracellular calcium stores only, and therefore the results suggest a direct activation of phospholipase C (27,28).…”

Section: Intracellular Calcium Phase 1 Extracellular Calcium Phase 2 mentioning

confidence: 56%

Effect of 2,4,6-trimethyl-N-[3-(trifluoromethyl)phenyl]benzene-sulfonamide on calcium influx in three contraction models

et al. 2015

Self Cite

View full text Add to dashboard Cite

2,4,6-Trimethyl--[3-(trifluoromethyl)phenyl]benzenesulfonamide (m-3M3FBS) activates phospholipase C and stimulates apoptosis; however, in smooth muscle cells it may increase the perfusion pressure. The main aim of the present study was to evaluate the physiological effect of direct stimulation of phospholipase C on vascular smooth muscle reactivity using three contraction models. Experiments were performed on the isolated and perfused tail artery of Wistar rats. The contraction force in the present model was measured by an increased level of perfusion pressure with a constant flow. Concentration-response curves (CRCs) obtained for phenylephrine, arg-vasopressin, mastoparan-7 and Bay K8644 presented a sigmoidal association. In comparison to the control curves, CRCs in the presence of m-3M3FBS were significantly shifted to the left except for Bay K8644. Analyses of calcium influx suggest that in the presence of m-3M3FBS the calcium influx from intra- and extracellular calcium stores was significantly higher. The results of the present experiments suggest that m-3M3FBS significantly increases the reactivity of vascular smooth muscle stimulated with metabotropic receptors or G-protein by an increase in calcium influx from intra- and extracellular calcium stores. The current knowledge regarding the apoptotic pathway shows the significance of calcium ions involved in this process, thus, m-3M3FBS may induce apoptosis by an increase of cytoplasmic calcium concentration; however, simultaneously, the use of this mechanism in therapy must be preceded by a molecular modification that eliminates a possible vasoconstriction effect.

show abstract

Role of acetylcholine and calcium ions in three vascular contraction models: Angiotensin II, phenylephrine and caffeine

Cited by 9 publications

References 20 publications

Caffeine Inhibits Acetylcholinesterase, But Not Butyrylcholinesterase

Caffeine Inhibits Acetylcholinesterase, But Not Butyrylcholinesterase

Cholinesterase targeting by polyphenols: A therapeutic approach for the treatment of Alzheimer’s disease

Effect of 2,4,6-trimethyl-N-[3-(trifluoromethyl)phenyl]benzene-sulfonamide on calcium influx in three contraction models

Contact Info

Product

Resources

About