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.

The role of transmembrane sodium gradient in rabbit ileal smooth muscle: Utilization of harmaline

1985 ◽  
Vol 5 (8) ◽  
pp. 667-671 ◽  
Author(s):  
M. S. Suleiman
Keyword(s):  
Smooth Muscle ◽  
Contractile Response ◽  
Sodium Concentration ◽  
Exchange Mechanism ◽  
Dependent Manner ◽  
Sodium Gradient ◽  
Extracellular Sodium ◽  
Dose Dependent

Decreasing extracellular sodium concentration was found to produce a contractile response of rabbit ileal smooth muscle. As the concentration decreases, the amplitude of contraction increases, thus producing a dose-dependent curve. Harmaline, a competitor for sodium, was found to inhibit the sodium gradient-dependent contractions in a dose-dependent manner. The results are interpreted as harmaline inhibiting a Na–Ca exchange mechanism present in ileal smooth muscle.

Role of catalase in the smooth muscle relaxant actions of sodium azide and cyanamide

2002 ◽  
Vol 435 (1) ◽  
pp. 93-101 ◽  
Author(s):  
Mohammad Shahidullah ◽  
Andrew Duncan ◽  
Peter D Stracħan ◽  
Komel M Rafique ◽  
Sarah L Ball ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Sodium Azide ◽  
Muscle Relaxant ◽  
Smooth Muscle Relaxant

Role of Intracellular Ca2+Stores in the Inhibitory Effect of Halothane on Airway Smooth Muscle Contraction 

1998 ◽  
Vol 89 (1) ◽  
pp. 165-173 ◽  
Author(s):  
Michiaki Yamakage ◽  
Shinji Kohro ◽  
Takashi Matsuzaki ◽  
Hideaki Tsuchida ◽  
Akoyoshi Namiki
Keyword(s):  
Smooth Muscle ◽  
Sarcoplasmic Reticulum ◽  
Airway Smooth Muscle ◽  
Muscle Tension ◽  
Inhibitory Effect ◽  
Intracellular Concentration ◽  
Dependent Manner ◽  
Release Channel ◽  
Dose Dependent

Background Halothane directly inhibits contraction of airway smooth muscle, mainly by decreasing the intracellular concentration of free Ca2+ ([Ca2+]i). The role of intracellular Ca2+ stores, sarcoplasmic reticulum, is still unclear. We investigated the role of sarcoplasmic reticulum in the inhibitory effect of halothane on contraction of airway smooth muscle by measuring [Ca2+]i and intracellular concentration of inositol 1,4,5-triphosphate ([IP3]i), a second messenger for release of Ca2+ from sarcoplasmic reticulum. Methods [Ca2+]i was monitored by measuring the 500-nm light emission ratio (F340/F380) of a Ca2+ indicator fura-2 with isometric tension of canine tracheal smooth muscle strip. During Ca2+-free conditions, carbachol (10(-5) M) was introduced with pretreatment of halothane (0-3%). During Ca2+-free conditions, 20 mM caffeine, a Ca2+-induced Ca2+ release channel opener, was introduced with or without halothane. We measured [IP3]i during exposure to carbachol and halothane by radioimmunoassay technique. Results Pretreatment with halothane significantly diminished carbachol-induced increases in [Ca2+]i by 77% and muscle tension by 83% in a dose-dependent manner. Simultaneous administration of halothane significantly enhanced caffeine-induced transient increases in [Ca2+]i and muscle tension in a dose-dependent manner, by 97% and 69%, respectively. Pretreatment with halothane abolished these responses. Rapid increase in [IP3]i produced by carbachol was significantly inhibited by 32% by halothane in a dose-dependent manner. Conclusions Halothane, during Ca2+-free conditions, inhibits transient contraction of airway smooth muscle induced by muscarinic receptor stimulation, mainly by attenuating the increase in [Ca2+]i. Depletion of Ca2+ from sarcoplasmic reticulum via Ca2+-induced Ca2+ release channels also may contribute to the attenuation of the increase in [Ca2+]i by halothane.

scholarly journals A Straight-Chain Alcohol Glycoside, with Smooth Muscle Relaxant Activity, from Rubus idaeus (Raspberry) Leaves

2007 ◽  
Vol 2 (9) ◽  
pp. 1934578X0700200 ◽  
Author(s):  
Asmita V. Patel ◽  
Christopher G. Dacke ◽  
Gerald Blunden ◽  
Janne Rojas Vera
Keyword(s):  
Smooth Muscle ◽  
Muscle Relaxant ◽  
Methanolic Extract ◽  
Rubus Idaeus ◽  
Straight Chain ◽  
Spectrometric Data ◽  
Muscle Relaxant Activity ◽  
Dose Dependent ◽  
Smooth Muscle Relaxant

A methanolic extract of Rubus idaeus leaves, when fractionated by column chromatography, yielded two distinct bands containing compounds that demonstrated in vitro, dose dependent, smooth muscle relaxant activity using transmurally-stimulated Guinea pig ileum preparations. From band two, following extensive chromatographic separation, several compounds with smooth muscle relaxant activity were obtained, one of which was characterized, from spectroscopic and mass spectrometric data, as 1- O-(1,2-dihydroxyethyl)-4- O-methoxy-β-D-glucopyranosyl-(1→3)-β-D-glucopyranoside.

scholarly journals Coptisine, a protoberberine alkaloid, relaxes mouse airway smooth muscle via blockade of VDLCCs and NSCCs

2020 ◽  
Vol 40 (2) ◽  
Author(s):  
Nana Wen ◽  
Lu Xue ◽  
Yongle Yang ◽  
Shunbo Shi ◽  
Qing-Hua Liu ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Muscle Contraction ◽  
Airway Smooth Muscle ◽  
Molecular Mechanisms ◽  
Force Measurement ◽  
Dependent Manner ◽  
Active Constituent ◽  
High K ◽  
Voltage Dependent

Abstract Background/Aims: Recently, effective and purified ingredients of traditional Chinese medicine (TCM) were extracted to play crucial roles in the treatment of pulmonary diseases. Our previous research focused on TCM drug screening aimed at abnormal airway muscle contraction during respiratory diseases. Coptisine, an effective ingredient extracted from bitter herbs has shown a series of antioxidant, antibacterial, cardioprotective and neuroprotective pharmacological properties. In the current study, we questioned whether coptisine could also participate in asthma treatment through relaxing abnormal contracted mouse airway smooth muscle (ASM). The present study aimed to characterize the relaxant effects of coptisine on mouse ASM and uncover the underlying molecular mechanisms. Methods: To investigate the role of coptisine on pre-contracted mouse ASM, a series of biological techniques, including force measurement and patch-clamp experiments were employed. Results: Coptisine was found to inhibit high K+ or acetylcholine chloride (ACh)-induced pre-contracted mouse tracheal rings in a dose-dependent manner. Further research demonstrated that the coptisine-induced mouse ASM relaxation was mediated by alteration of calcium mobilization via voltage-dependent L-type Ca2+ channels (VDLCCs) and non-selective cation channels (NSCCs). Conclusion: Our data showed that mouse ASM could be relaxed by coptisine via altering the intracellular Ca2+ concentration through blocking VDLCCs and NSCCs, which suggested that this pharmacological active constituent might be classified as a potential new drug for the treatment of abnormal airway muscle contraction.

Abstract P210: (Pro)Renin Receptor Regulates Potassium Homeostasis via Intrarenal Aldosterone

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Chuanming Xu ◽  
Aihua Lu ◽  
Hong Wang ◽  
Hui Fang ◽  
Li Zhou ◽  
...  
Keyword(s):  
Protein Expression ◽  
Potential Role ◽  
Fold Increase ◽  
Dependent Manner ◽  
Sd Rats ◽  
High K ◽  
Functional Implications ◽  
Calcium Activated Potassium Channel ◽  
Dose Dependent

It has been shown that transgenic overexpression of human (pro)renin receptor (PRR) results in elevated aldosterone (Aldo) level with unclear functional implications. The present study examined a potential role of renal PRR during high K + (HK) loading. In normal SD rats, a 1-week HK intake (5% KCl in diet) induced a 3.4-fold increase in renal protein expression of full-length PRR and 4.2-fold increase in urinary excretion of soluble PRR (sPRR). Administration of PRO20, a decoy peptide antagonist of PRR, at 700 μg/kg/d via i.p. injections, to K + -loaded animals elevated plasma K + level (5.72+0.08 vs. 4.84±0.18 mM, p<0.05) and decreased urinary K + excretion (2.52+0.11 vs. 3.43+0.19 mmol/24h, p<0.05), accompanied with a 26.2% reduction of urinary aldosterone (Aldo) excretion. HK downregulated NCC protein expression (57.8%) and upregulated renal protein expression of aldosterone synthase CYP11B2 (229%), ROMK (156%), calcium-activated potassium channel subunit alpha-1 (α-BK) (367%), α-Na + -K + -ATPase (596%), and β-ENaC (155%), all of which were significantly blunted by PRO20 (by 50 - 70%). The same maneuvers were applied to adrenalectomized (ADX) rats. Although plasma Aldo was extremely low and also unresponsive to HK loading, urinary Aldo excretion was elevated by 274% with this treatment, which was abolished by PRO20. The HK-induced responses of the above K + and Na + transporting proteins in ADX rats all persisted and also remained sensitive to PRO20. Additionally, spironolactone treatment in ADX rats was still effective in inhibiting kaliuresis induced by HK loading, resulting in hyperkalemia (Plasma K+: 5.13±0.07 vs. 4.19±0.27 mM, p<0.05). In primary rat IMCD cells, exposure to 10 mM KCl for 24 h augmented PRR protein expression and sPRR release in a time- and dose-dependent manner. HK upregulated Aldo release in parallel with increased CYP11B2 protein expression, which were both attenuated by PRO20 or PRR siRNA. A recombinant sPRR, sPRR-His, stimulated Aldo release and CYP11B2 expression. Taken together, we conclude that HK increased renal PRR expression that stimulates renal synthesis of Aldo that coordinates the response of renal membrane Na + and K + transporting proteins to facilitate K + secretion.

Norepinephrine-induced contraction of isolated rabbit bronchial artery: role of α1- and α2-adrenoceptor activation

1997 ◽  
Vol 82 (6) ◽  
pp. 1918-1925 ◽  
Author(s):  
A. O. A. Zschauer ◽  
M. W. Sielczak ◽  
D. A. S. Smith ◽  
A. Wanner
Keyword(s):  
Smooth Muscle ◽  
Response Curve ◽  
Bronchial Artery ◽  
No Synthase ◽  
Dependent Manner ◽  
Cyclooxygenase Inhibitor ◽  
Synthase Inhibitor ◽  
The Right ◽  
Dose Dependent

Zschauer, A. O. A., M. W. Sielczak, D. A. S. Smith, and A. Wanner. Norepinephrine-induced contraction of isolated rabbit bronchial artery: role of α1- and α2-adrenoceptor activation. J. Appl. Physiol. 82(6): 1918–1925, 1997.—The contractile effect of norepinephrine (NE) on isolated rabbit bronchial artery rings (150–300 μm in diameter) and the role of α1- and α2-adrenoceptors (AR) on smooth muscle and endothelium were studied. In intact arteries, NE increased tension in a dose-dependent manner, and the sensitivity for NE was further increased in the absence of endothelium. In intact but not in endothelium-denuded arteries, the response to NE was increased in the presence of both indomethacin (Indo; cyclooxygenase inhibitor) and N G-nitro-l-arginine methyl ester [l-NAME; nitric oxide (NO) synthase inhibitor], indicating that two endothelium-derived factors, NO and a prostanoid, modulate the NE-induced contraction. The α1-AR antagonist prazosin shifted the NE dose-response curve to the right, and phenylephrine (α1-AR agonist) induced a dose-dependent contraction that was potentiated byl-NAME or removal of the endothelium. The sensitivity to NE was increased slightly by the α2-AR antagonists yohimbine and idazoxan, and this effect was abolished by Indo or removal of the endothelium. Similarly, contractions induced by UK-14304 (α2-AR agonist) were potentiated by Indo or removal of the endothelium. These results suggest that NE-induced contraction is mediated through activation of α1- and α2-ARs on both smooth muscle and endothelium. Activation of the α1- and α2-ARs on the smooth muscle causes contraction, whereas activation of the endothelial α1- and α2-ARs induces relaxation through release of NO (α1-ARs) and a prostanoid (α2-ARs).

Amelioration of Carbon Tetrachloride-Induced Liver Injury by Citrus Leaf Extract

2019 ◽  
Vol 17 (4) ◽  
pp. 426-431
Author(s):  
Jin Xuezhu ◽  
Li Jitong ◽  
Nie Leigang ◽  
Xue Junlai
Keyword(s):  
Carbon Tetrachloride ◽  
Leaf Extract ◽  
Hepatic Injury ◽  
The Body ◽  
Dependent Manner ◽  
Weight Changes ◽  
Citrus Leaf ◽  
Dose Dependent ◽  
And Oxidative Stress

The main purpose of this study is to investigate the role of citrus leaf extract in carbon tetrachloride-induced hepatic injury and its potential molecular mechanism. Carbon tetrachloride was used to construct hepatic injury animal model. To this end, rats were randomly divided into 4 groups: control, carbon tetrachloride-treated, and two carbon tetrachloride + citrus leaf extract-treated groups. The results show that citrus leaf extract treatment significantly reversed the effects of carbon tetrachloride on the body weight changes and liver index. Besides, treatment with citrus leaf extract also reduced the levels of serum liver enzymes and oxidative stress in a dose-dependent manner. H&E staining and western blotting suggested that citrus leaf extract could repair liver histological damage by regulating AMPK and Nrf-2.

scholarly journals Lumican Inhibits Osteoclastogenesis and Bone Resorption by Suppressing Akt Activity

2021 ◽  
Vol 22 (9) ◽  
pp. 4717
Author(s):  
Jin-Young Lee ◽  
Da-Ae Kim ◽  
Eun-Young Kim ◽  
Eun-Ju Chang ◽  
So-Jeong Park ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Bone Formation ◽  
Map Kinases ◽  
Osteoclast Differentiation ◽  
Dependent Manner ◽  
Dual Action ◽  
Dose Dependent ◽  
Resorptive Activity

Lumican, a ubiquitously expressed small leucine-rich proteoglycan, has been utilized in diverse biological functions. Recent experiments demonstrated that lumican stimulates preosteoblast viability and differentiation, leading to bone formation. To further understand the role of lumican in bone metabolism, we investigated its effects on osteoclast biology. Lumican inhibited both osteoclast differentiation and in vitro bone resorption in a dose-dependent manner. Consistent with this, lumican markedly decreased the expression of osteoclastogenesis markers. Moreover, the migration and fusion of preosteoclasts and the resorptive activity per osteoclast were significantly reduced in the presence of lumican, indicating that this protein affects most stages of osteoclastogenesis. Among RANKL-dependent pathways, lumican inhibited Akt but not MAP kinases such as JNK, p38, and ERK. Importantly, co-treatment with an Akt activator almost completely reversed the effect of lumican on osteoclast differentiation. Taken together, our findings revealed that lumican inhibits osteoclastogenesis by suppressing Akt activity. Thus, lumican plays an osteoprotective role by simultaneously increasing bone formation and decreasing bone resorption, suggesting that it represents a dual-action therapeutic target for osteoporosis.

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