Nuciferine Relaxes Tracheal Rings via the Blockade of VDLCC and NSCC Channels

Planta Medica ◽  
2017 ◽  
Vol 84 (02) ◽  
pp. 83-90 ◽  
Author(s):  
Xiao Yang ◽  
Meng-Fei Yu ◽  
Jun Lei ◽  
Yong-Bo Peng ◽  
Ping Zhao ◽  
...  
Keyword(s):  
Muscle Tone ◽  
Smooth Muscles ◽  
Cation Channels ◽  
Dependent Manner ◽  
Aporphine Alkaloid ◽  
Nonselective Cation Channels ◽  
High K ◽  
Voltage Dependent ◽  
Resting Muscle ◽  
Dose Dependent

AbstractThis study aimed to elucidate the mechanisms of nuciferine (a main aporphine alkaloid of lotus leaf extract), which can induce relaxation in contracted tracheal rings. Under Ca2+-free and 2 mM Ca2+ conditions, we found that nuciferine had no effect on the resting muscle tone of tracheal rings. In contrast, nuciferine relaxed high K+-contracted mouse tracheal rings in a dose-dependent manner and inhibited both Ca2+ influx and voltage-dependent L-type Ca2+ channel currents induced by high K+. Similarly, nuciferine also inhibited acetylcholine-induced contractions in mouse tracheal rings in a dose-dependent manner. Meanwhile, both acetylcholine-induced intracellular Ca2+ influx and whole-cell currents of nonselective cation channels were blocked by nuciferine. Together, the results indicate that nuciferine-induced relaxation in tracheal rings mainly occurred due to the inhibition of extracellular Ca2+ influx through the blockade of voltage-dependent L-type Ca2+ channels and/or nonselective cation channels. These results suggest that nuciferine has a therapeutic effect on respiratory diseases associated with the aberrant contraction of airway smooth muscles and/or bronchospasm.

Histamine-induced depolarization: ionic mechanisms and role in sustained contraction of rabbit cerebral arteries

2000 ◽  
Vol 278 (6) ◽  
pp. H2094-H2104 ◽  
Author(s):  
N. I. Gokina ◽  
J. A. Bevan
Keyword(s):  
Isometric Force ◽  
Cerebral Arteries ◽  
Cation Channels ◽  
Sustained Contraction ◽  
Nonselective Cation Channels ◽  
High K ◽  
Voltage Dependent ◽  
Ionic Mechanisms ◽  
A Minor

The role of membrane depolarization in the histamine-induced contraction of the rabbit middle cerebral artery was examined by simultaneous measurements of membrane potential and isometric force. Histamine (1–100 μM) induced a concentration-dependent sustained contraction associated with sustained depolarization. Action potentials were observed during depolarization caused by histamine but not by high-K+ solution. K+-induced contraction was much smaller than sustained contraction associated with the same depolarization caused by histamine. Nifedipine attenuates histamine-induced sustained contraction by 80%, with no effect on depolarization. Inhibition of nonselective cation channels with Co2+ (100–200 μM) reversed the histamine-induced depolarization and relaxed the arteries but induced only a minor change in K+-induced contraction. In the presence of Co2+ and in low-Na+solution, histamine-evoked depolarization and contraction were transient. We conclude that nonselective cation channels contribute to histamine-induced sustained depolarization, which stimulates Ca2+ influx through voltage-dependent Ca2+channels participating in contraction. The histamine-induced depolarization, although an important and necessary mechanism, cannot fully account for sustained contraction, which may be due in part to augmentation of currents through voltage-dependent Ca2+channels and Ca2+ sensitization of the contractile process.

Polydatin Attenuates Carbachol-induced Contraction of Guinea Pig Gallbladder

2019 ◽  
Vol 18 (1) ◽  
pp. 34-38
Author(s):  
Chen Lei ◽  
Pan Xiang ◽  
Shen Yonggang ◽  
Song Kai ◽  
Zhong Xingguo ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Guinea Pig ◽  
Smooth Muscles ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Cyclic Guanosine Monophosphate ◽  
Guanosine Monophosphate ◽  
Dependent Manner ◽  
Underlying Mechanisms ◽  
Dose Dependent

The aim of this study was to determine whether polydatin, a glucoside of resveratrol isolated from the root of Polygonum cuspidatum, warranted development as a potential therapeutic for ameliorating the pain originating from gallbladder spasm disorders and the underlying mechanisms. Guinea pig gallbladder smooth muscles were treated with polydatin and specific inhibitors to explore the mechanisms underpinning polydatin-induced relaxation of carbachol-precontracted guinea pig gallbladder. Our results shown that polydatin relaxed carbachol-induced contraction in a dose-dependent manner through the nitric oxide/cyclic guanosine monophosphate/protein kinase G and the cyclic adenosine monophosphate/protein kinase A signaling pathways as well as the myosin light chain kinase and potassium channels. Our findings suggested that there was value in further exploring the potential therapeutic use of polydatin in gallbladder spasm disorders.

Role of extracellular calcium and calmodulin in prolactin secretion induced by hyposmolarity, thyrotropin-releasing hormone, and high K+ in GH4C1 cells

1990 ◽  
Vol 123 (2) ◽  
pp. 218-224 ◽  
Author(s):  
Xiangbing Wang ◽  
Noriyuki Sato ◽  
Monte A. Greer ◽  
Susan E. Greer ◽  
Staci McAdams
Keyword(s):  
Smooth Muscle ◽  
Muscle Relaxant ◽  
Prolactin Secretion ◽  
Thyrotropin Releasing Hormone ◽  
Dependent Manner ◽  
Cell Toxicity ◽  
High K ◽  
Dose Dependent ◽  
Smooth Muscle Relaxant

Abstract. The mechanism by which 30% medium hyposmolarity induces PRL secretion by GH4C1 cells was compared with that induced by 100 nmol/l TRH or 30 mmol/l K+. Removing medium Ca2+, blocking Ca2+ channels with 50 μmol/l verapamil, or inhibiting calmodulin activation with 20 μmol/l trifluoperazine, 10 μmol/l chlorpromazine or 10 μmol/l pimozide almost completely blocked hyposmolarity-induced secretion. The smooth muscle relaxant, W-7, which is believed relatively specific in inhibiting the Ca2+-calmodulin interaction, depressed hyposmolarity-induced PRL secretion in a dose-dependent manner (r = −0.991, p<0.01 ). The above drugs also blocked or decreased high K+-induced secretion, but had much less effect on TRH-induced secretion. Secretion induced by TRH, hyposmolarity, or high K+ was optimal at pH 7.3-7.65 and was significantly depressed at pH 6.0 or 8.0, indicating that release of hormone induced by all 3 stimuli is due to an active cell process requiring a physiologic extracellular pH and is not produced by nonspecific cell toxicity. The data suggest hyposmolarity and high K+ may share some similarities in their mechanism of stimulating secretion, which is different from that of TRH.

Vascular Angiotensin-Converting Enzyme Activity in Man and other Species

1984 ◽  
Vol 66 (1) ◽  
pp. 39-45 ◽  
Author(s):  
Mizuo Miyazaki ◽  
Hideki Okunishi ◽  
Kazuo Nishimura ◽  
Noboru Toda
Keyword(s):  
Angiotensin Converting Enzyme ◽  
High Performance ◽  
Muscle Tone ◽  
Chloride Ion ◽  
Kidney Cortex ◽  
Dependent Manner ◽  
Converting Enzyme ◽  
Aortic Endothelial Cells ◽  
Ace Activity ◽  
Dose Dependent

1. Angiotensin-converting enzyme (ACE) activity in blood vessels of different species was determined. 2. ACE was solubilized by Nonidet P-40, and assayed by reversible phase high performance liquid chromatography. Approximately 98% ACE was recovered in the liquid phase by the use of the detergent. 3. The ACE activity varied with chloride ion (Cl−) concentrations; the maximum activities in dog, human, monkey and rabbit tissues were obtained at the concentrations of 800, 600, 600 and 300 mmol/l respectively. The optimal Cl− concentration was quite similar in different tissues and plasma obtained from the same species. 4. The ACE activity in the cerebral, mesenteric, pulmonary and renal arteries was in a range between 1.01 and 1.60 m-units/mg of protein in dogs and between 0.43 and 0.94 m-unit/mg of protein in monkeys. The activity in dog aortae was 0.20 ± 0.02 m-unit/mg of protein, and the activity in aortic endothelial cells was 2.61 ± 0.65 m-units/mg of protein. ACE activities in the dog lung, kidney cortex and cerebral cortex were 28.6 ± 2.6, 15.7 ± 3.0 and 3.5 ± 0.6m-units/mg of protein respectively. SA-446, a captopril-like ACE inhibitor, reduced the ACE activity in arteries in a dose-dependent manner. 5. Vascular ACE appears to be concentrated in the endothelium and may contribute to regulate vascular muscle tone and local blood flow by a conversion of angiotensin I into II.

Benzodiazepines Block α2-Containing Inhibitory Glycine Receptors in Embryonic Mouse Hippocampal Neurons

2003 ◽  
Vol 90 (1) ◽  
pp. 89-99 ◽  
Author(s):  
Liu Lin Thio ◽  
Ananth Shanmugam ◽  
Keith Isenberg ◽  
Kelvin Yamada
Keyword(s):  
Hippocampal Neurons ◽  
Clinical Effects ◽  
Dependent Manner ◽  
Glycine Receptors ◽  
Binding Studies ◽  
Chloride Currents ◽  
Embryonic Mouse ◽  
Voltage Dependent ◽  
Polymerase Chain ◽  
Dose Dependent

Inhibitory glycine receptors (GlyRs) in the mammalian cortex probably contribute to brain development and to maintaining tonic inhibition. Given their presence throughout the cortex, their modulation likely has important physiological consequences. Although benzodiazepines potentiate γ-aminobutyric acidA receptors (GABAARs), they may also modulate GlyRs because binding studies initially suggested that they act at GlyRs. Furthermore, their diminished ability to potentiate neonatal GABAARs suggests that they may exert their beneficial clinical effects at another site in the developing brain. Therefore we examined the effect of benzodiazepines on whole cell currents mediated by GlyRs in cultured embryonic mouse hippocampal neurons. First, we determined the GlyR subunit composition in this preparation. Glycine, β-alanine, and taurine activate strychnine-sensitive chloride currents in a dose-dependent manner. Maximal concentrations of the three agonists produce equal, nonadditive responses as expected of full agonists. The pharmacological properties of the GlyR currents including their pattern of modulation by picrotoxinin, picrotin, and tropisetron indicate that GlyRs consist of α2β heteromers and α2 homomers. Reverse transcriptase polymerase chain reaction (RTPCR) studies confirmed the presence of α2 and β subunits. Second, we found that micromolar concentrations of some benzodiazepines, including chlordiazepoxide and nitrazepam, inhibit GlyR currents. Nitrazepam inhibition of GlyRs is noncompetitive, is not voltage dependent, and does not reflect enhanced desensitization. Thus benzodiazepines allosterically inhibit α2-containing GlyRs in embryonic mouse hippocampal neurons via a “low”-affinity site.

Hormone-induced rise in cytosolic Ca2+ in axolotl hepatocytes: properties of the Ca2+ influx channel

1997 ◽  
Vol 273 (5) ◽  
pp. C1526-C1532 ◽  
Author(s):  
Thomas Lenz ◽  
Jochen W. Kleineke
Keyword(s):  
Inhibitory Concentration ◽  
Cation Channels ◽  
Strong Inhibition ◽  
Michaelis Constant ◽  
Cyclic Monophosphate ◽  
First Order ◽  
First Order Kinetics ◽  
Nonselective Cation Channels ◽  
Store Depletion ◽  
Voltage Dependent

Calcium entry in nonexcitable cells occurs through Ca2+-selective channels activated secondarily to store depletion and/or through receptor- or second messenger-operated channels. In amphibian liver, hormones that stimulate the production of adenosine 3′,5′-cyclic monophosphate (cAMP) also regulate the opening of an ion gate in the plasma membrane, which allows a noncapacitative inflow of Ca2+. To characterize this Ca2+ channel, we studied the effects of inhibitors of voltage-dependent Ca2+ channels and of nonselective cation channels on 8-bromoadenosine 3′,5′-cyclic monophosphate (8-BrcAMP)-dependent Ca2+ entry in single axolotl hepatocytes. Ca2+ entry provoked by 8-BrcAMP in the presence of physiological Ca2+ followed first-order kinetics (apparent Michaelis constant = 43 μM at the cell surface). Maximal values of cytosolic Ca2+ (increment ∼300%) were reached within 15 s, and the effect was transient (half time of 56 s). We report a strong inhibition of cAMP-dependent Ca2+ entry by nifedipine [half-maximal inhibitory concentration (IC50) = 0.8 μM], by verapamil (IC50 = 22 μM), and by SK&F-96365 (IC50 = 1.8 μM). Depolarizing concentrations of K+were without effect. Gadolinium and the anti-inflammatory compound niflumate, both inhibitors of nonselective cation channels, suppressed Ca2+ influx. This “profile” indicates a novel mechanism of Ca2+ entry in nonexcitable cells.

Vasodilation induced by substance P in guinea pig carotid arteries

1994 ◽  
Vol 266 (3) ◽  
pp. H1132-H1137
Author(s):  
G. Zhang ◽  
Y. Yamamoto ◽  
K. Miwa ◽  
H. Suzuki
Keyword(s):  
Substance P ◽  
Guinea Pig ◽  
Carotid Arteries ◽  
Smooth Muscles ◽  
Peak Amplitude ◽  
Resting Potential ◽  
Dependent Manner ◽  
Similar Form ◽  
Concentration Dependent Manner ◽  
High K

In the guinea pig carotid artery with an intact endothelium, substance P (SP, 10(-10)-10(-7) M) relaxed the norepinephrine- (NE) contracted smooth muscles transiently, in a concentration-dependent manner. Acetylcholine (ACh, 10(-6) M) produced a sustained relaxation. SP and ACh also relaxed muscles contracted with high-K (29.6 mM) solution, with a similar form but with a reduced amplitude compared with findings in NE-contracted muscles. In the presence of nitroarginine (10(-5) M) and NE, the ACh-induced relaxation was transient, with a reduced amplitude, whereas the SP-induced relaxation was not significantly changed. In muscles contracted with high-K solution containing nitroarginine, neither SP nor ACh produced relaxation. SP (> 10(-11) M) transiently hyperpolarized the membrane, but only when this peptide was applied from the intimal side of the intact vessel, and the peak amplitude reached approximately 20 mV from the resting potential at 10(-8) M. ACh transiently hyperpolarized the membrane (the peak amplitude being approximately 10 mV), in both the adventitial and intimal applications. In high-K solution, neither SP nor ACh produced hyperpolarization. The amplitude of hyperpolarizations produced by SP did not significantly change in the presence of nitroarginine, oxyhemoglobin, or indomethacin. Thus, SP-induced relaxation seems to be produced mainly by endothelium-derived hyperpolarizing factor-induced hyperpolarization.

scholarly journals Relaxant Action ofPlumula NelumbinisExtract on Mouse Airway Smooth Muscle

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Li Tan ◽  
Weiwei Chen ◽  
Ming-Yu Wei ◽  
Jinhua Shen ◽  
Meng-Fei Yu ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Biological Activities ◽  
Chloroform Extract ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Resting Tension ◽  
High K ◽  
Voltage Dependent ◽  
Anti Inflammation

The traditional herbPlumula Nelumbinisis widely used in the world because it has many biological activities, such as anti-inflammation, antioxidant, antihypertension, and butyrylcholinesterase inhibition. However, the action ofPlumula Nelumbinison airway smooth muscle (ASM) relaxation has not been investigated. A chloroform extract ofPlumula Nelumbinis(CEPN) was prepared, which completely inhibited precontraction induced by high K+in a concentration-dependent manner in mouse tracheal rings, but it had no effect on resting tension. CEPN also blocked voltage-dependent L-type Ca2+channel- (VDCC-) mediated currents. In addition, ACh-induced precontraction was also completely blocked by CEPN and partially inhibited by nifedipine or pyrazole 3. Besides, CEPN partially reduced ACh-activated nonselective cation channel (NSCC) currents. Taken together, our data demonstrate that CEPN blocked VDCC and NSCC to inhibit Ca2+influx, resulting in relaxation of precontracted ASM. This finding indicates that CEPN would be a candidate of new potent bronchodilators.

Phorbol-stimulated influx of extracellular calcium in rat pulmonary artery endothelial cells

1994 ◽  
Vol 267 (2) ◽  
pp. L145-L151 ◽  
Author(s):  
H. S. Murphy ◽  
M. Maroughi ◽  
G. O. Till ◽  
P. A. Ward
Keyword(s):  
Endothelial Cells ◽  
Pulmonary Artery ◽  
Extracellular Calcium ◽  
Dependent Manner ◽  
Necrosis Factor Alpha ◽  
Calcium Dependent ◽  
High K ◽  
Voltage Dependent ◽  
Dependent Inhibition ◽  
Protein Kinase C Inhibitor

Stimulation of rat pulmonary artery endothelial cells (RPAEC) with phorbol 12-myristate 13-acetate (PMA) resulted in an increase in intracellular calcium ([Ca2+]i). Unlike the response to bradykinin, C5a and tumor necrosis factor-alpha (TNF-alpha) previously reported (15), the PMA-induced increase in [Ca2+]i was predominantly dependent on extracellular calcium. The PMA response paralleled the BAY K 8644-induced, extracellular calcium-dependent increase in [Ca2+]i. Pretreatment of endothelial cells with the protein kinase C inhibitor staurosporine resulted in a concentration-dependent inhibition of the increase in [Ca2+]i in response to PMA. The ability of PMA analogues to induce significant increase in [Ca2+]i paralleled their ability to induce O2- generation in neutrophils. The PMA-induced influx of extracellular Ca2+ was inhibited by the L-channel selective antagonists diltiazem, nifedipine, nicardipine, and verapamil in a dose-dependent manner. Depolarizing conditions induced by high [K+]o enhanced the calcium response to PMA. The data presented are consistent with the hypothesis that PMA-induced increases in [Ca2+]i in endothelial cells are the result of Ca2+ influx through voltage-dependent L-type Ca2+ channels.

scholarly journals Inhibition of light-induced stomatal opening by allyl isothiocyanate does not require guard cell cytosolic Ca2+ signaling

2020 ◽  
Vol 71 (10) ◽  
pp. 2922-2932 ◽  
Author(s):  
Wenxiu Ye ◽  
Eigo Ando ◽  
Mohammad Saidur Rhaman ◽  
Md Tahjib-Ul-Arif ◽  
Eiji Okuma ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Stomatal Closure ◽  
Allyl Isothiocyanate ◽  
Stomatal Opening ◽  
Cation Channels ◽  
Dependent Manner ◽  
Defense System ◽  
Independent Manner ◽  
Dose Dependent

Abstract The glucosinolate–myrosinase system is a well-known defense system that has been shown to induce stomatal closure in Brassicales. Isothiocyanates are highly reactive hydrolysates of glucosinolates, and an isothiocyanate, allyl isothiocyanate (AITC), induces stomatal closure accompanied by elevation of free cytosolic Ca2+ concentration ([Ca2+]cyt) in Arabidopsis. It remains unknown whether AITC inhibits light-induced stomatal opening. This study investigated the role of Ca2+ in AITC-induced stomatal closure and inhibition of light-induced stomatal opening. AITC induced stomatal closure and inhibited light-induced stomatal opening in a dose-dependent manner. A Ca2+ channel inhibitor, La3+, a Ca2+chelator, EGTA, and an inhibitor of Ca2+ release from internal stores, nicotinamide, inhibited AITC-induced [Ca2+]cyt elevation and stomatal closure, but did not affect inhibition of light-induced stomatal opening. AITC activated non-selective Ca2+-permeable cation channels and inhibited inward-rectifying K+ (K+in) channels in a Ca2+-independent manner. AITC also inhibited stomatal opening induced by fusicoccin, a plasma membrane H+-ATPase activator, but had no significant effect on fusicoccin-induced phosphorylation of the penultimate threonine of H+-ATPase. Taken together, these results suggest that AITC induces Ca2+ influx and Ca2+ release to elevate [Ca2+]cyt, which is essential for AITC-induced stomatal closure but not for inhibition of K+in channels and light-induced stomatal opening.

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