• The Korean Journal of Physiology
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• v.23 no.1
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• pp.99-108
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• 1989

The effects of prostaglandin $(PGF_{2{\alpha}})$ on the contractility of vascular smooth muscle were investigated in the helical strip of the rabbit aorta. The aortic strip was immersed in the phosphate-buffered Tyrode's solution which was equilibrated with 100% $O_{2}$ at $35^{\circ}C$ and its isometric tension was measured. The contraction was induced by $(PGF_{2{\alpha}})$, norepinephrine (NE), or potassium (40 mM) in the nomal Tyrode's solution (1 mM, $Ca^{2+}$) or $Ca^{2+}-free$ Tyrode's solution. Effects of verapamil and phentolamine on the contraction were also observed. The aortic strip began to contract at the concentration of $5\;{\mu}g%$ and reached the maximal contraction at the concentration of $150\;{\mu}g%$ $(PGF_{2{\alpha}})$. The maximal contraction was corresponded respectively to $52.2{\pm}3.0%$ and $81.5{\pm}3.5%$ of maximal contraction by NE $(1{\times}10^{-5}M)$ and 40 mM $K^{+}$. And the maximal contractions by $(PGF_{2{\alpha}})$ or NE were induced at the concentration of about 1 mM $Ca^{2+}$. $(PGF_{2{\alpha}})$ induced the contraction of aortic strip even after induction of contraction by 40 mM $K^{+}$ and the contraction by $(PGF_{2{\alpha}})$ was not blocked by the ${\alpha}-receptor$ blocker, phentolamine. And the contraction by the $(PGF_{2{\alpha}})$ was inhibited partially by a verapamil at the concentration of $1{\times}10^{-5}M$ and the contraction began to increase at the concentration of $1{\times}10^{-4}M$ verapamil. Whereas the contraction by NE was completely blocked by verapamil. Though both the $(PGF_{2{\alpha}})$ and NE induced the contraction in the $Ca^{2+}-free$ Tyrode's solution, the peak tension was not maintained. But the rate of tension decline was lower in the contraction by $(PGF_{2{\alpha}})$ than in that by NE. The verapamil did not inhibit the contraction by $(PGF_{2{\alpha}})$ in the $Ca^{2+}-free$ Tyrode's solution and increased the contraction at the concentration of above $1{\times}10^{-4}M$. The NE-induced contraction in the $Ca^{2+}-free$ Tyrode's solution was inhibited completely by a verapamil. From the above results it is suggested that the contraction induced by $(PGF_{2{\alpha}})$ results from the promotion of the both $Ca^{2+}$ influx and the intracellular $Ca^{2+}$ release by different way from NE.

• Journal of Microbiology and Biotechnology
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• v.30 no.5
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• pp.649-661
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• 2020

This study examined the laxative effects of hot-water extracts of Hovenia dulcis Thunb. (HD), Phyllostachys pubescens Mazel (PM), and a 2:8 mixture of both (HP) in two chronic constipation models. For the loperamide-induced constipation model, animals were divided into an untreated group, negative control group (loperamide 4 mg/kg), positive control group (bisacodyl 4 mg/kg) group, and six treatment groups (HP 100 or 400, HD 50 or 100, and PM 100 or 400 mg/kg). For the low-fiber diet-induced constipation model, animals were divided into an untreated group (normal diet), negative control group (low-fiber diet), positive control group (Agio granule, 620 mg/kg), and the same treatment groups. Fecal number, weight, fecal water content, and intestinal transit ratio were higher in the groups treated with HP, HD, and PM than in the groups treated with loperamide or low-fiber diet. Thickness of colon mucosa and muscle layers were increased in the treated groups. Colon tension increased in the HP groups, and [Ca²⁺]i measurements using fura-2 as an indicator showed that HP inhibits ATP-mediated Ca²⁺ influx in IEC-18 cells. These results showed that the HP mixture has laxative activity by increased mucin secretion and inducing contractile activity and relaxation. It may be a useful therapeutic strategy for ameliorating in chronic constipation.

• The Korean Journal of Physiology and Pharmacology
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• v.14 no.4
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• pp.241-248
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• 2010

The present sutdy aimed to determine whether olmesartan, an angiotensin II (Ang II) type 1 ($AT_1$) receptor blocker, can influence the CA release from the isolated perfused model of the rat adrenal medulla. Olmesartan ($5{\sim}50{\mu}M$) perfused into an adrenal vein for 90 min produced dose- and time-dependent inhibition of the CA secretory responses evoked by ACh (5.32 mM), high $K^+$ (56 mM, a direct membrane-depolarizer), DMPP (100 ${\mu}M$) and McN-A-343 (100 ${\mu}M$). Olmesartan did not affect basal CA secretion. Also, in adrenal glands loaded with olmesartan (15 ${\mu}M$), the CA secretory responses evoked by Bay-K-8644 (10 ${\mu}M$, an activator of voltage-dependent L-type $Ca^{2+}$ channels), cyclopiazonic acid (10 ${\mu}M$, an inhibitor of cytoplasmic $Ca^{2+}$-ATPase), veratridine (100 ${\mu}M$, an activator of voltage-dependent $Na^+$ channels), and Ang II (100 nM) were markedly inhibited. However, at high concentrations ($150{\sim}300{\mu}M$), olmesartan rather enhanced the ACh-evoked CA secretion. Taken together, these results show that olmesartan at low concentrations inhibits the CA secretion evoked by cholinergic stimulation (both nicotininc and muscarinic receptors) as well as by direct membrane depolarization from the rat adrenal medulla, but at high concentrations it rather potentiates the ACh-evoked CA secretion. It seems that olmesartan has a dual action, acting as both agonist and antagonist at nicotinic receptors of the isolated perfused rat adrenal medulla, which might be dependent on the concentration. It is also thought that this inhibitory effect of olmesartan may be mediated by blocking the influx of both $Na^+$ and $Ca^{2+}$ into the rat adrenomedullary chromaffin cells as well as by inhibiting the $Ca^{2+}$ release from the cytoplasmic calcium store, which is thought to be relevant to the $AT_1$ receptor blockade, in addition to its enhancement on the CA secreton.

• The Korean Journal of Physiology and Pharmacology
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• v.12 no.3
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• pp.101-109
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• 2008

The aim of the present study was to examine the effects of ketamine, a dissociative anesthetics, on secretion of catecholamines (CA) secretion evoked by cholinergic stimulation from the perfused model of the isolated rat adrenal gland, and to establish its mechanism of action, and to compare ketamine effect with that of thiopental sodium, which is one of intravenous barbiturate anesthetics. Ketamine ($30{\sim}300{\mu}M$), perfused into an adrenal vein for 60 min, dose- and time-dependently inhibited the CA secretory responses evoked by ACh (5.32 mM), high $K^+$ (a direct membrane-depolarizer, 56 mM), DMPP (a selective neuronal nicotinic NN receptor agonist, $100{\mu}M$) and McN-A-343 (a selective muscarinic M1 receptor agonist, $100{\mu}M$). Also, in the presence of ketamine ($100{\mu}M$), the CA secretory responses evoked by veratridine (a voltage-dependent $Na^+$ channel activator, $100{\mu}M$), Bay-K-8644 (an L-type dihydropyridine $Ca^{2+}$ channel activator, $10{\mu}M$), and cyclopiazonic acid (a cytoplasmic $Ca^{2+}$-ATPase inhibitor, $10{\mu}M$) were significantly reduced, respectively. Interestingly, thiopental sodium ($100{\mu}M$) also caused the inhibitory effects on the CA secretory responses evoked by ACh, high $K^+$, DMPP, McN-A-343, veratridine, Bay-K-8644, and cyclopiazonic acid. Collectively, these experimental results demonstrate that ketamine inhibits the CA secretion evoked by stimulation of cholinergic (both nicotinic and muscarinic) receptors and the membrane depolarization from the isolated perfused rat adrenal gland. It seems likely that the inhibitory effect of ketamine is mediated by blocking the influx of both $Ca^{2+}$ and $Na^+$ through voltage-dependent $Ca^{2+}$ and $Na^+$ channels into the rat adrenal medullary chromaffin cells as well as by inhibiting $Ca^{2+}$ release from the cytoplasmic calcium store, which are relevant to the blockade of cholinergic receptors. It is also thought that, on the basis of concentrations, ketamine causes similar inhibitory effect with thiopental in the CA secretion from the perfused rat adrenal medulla.

• The Korean Journal of Physiology and Pharmacology
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• v.6 no.4
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• pp.215-223
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• 2002

The present study was undertaken to investigate the effect of doxorubicin (DX) on secretion of catecholamines (CA) evoked by ACh, high $K^+,$ DMPP and McN-A-343 from the isolated perfused rat adrenal gland and to establish the mechanism of its action. DX $(10^{-7}{\sim}10^{-6}\;M)$ perfused into an adrenal vein for 60 min produced relatively dose- and time-dependent inhibition of CA secretory responses evoked by ACh $(5.32{\times}10^{-3}\;M),$ DMPP $(10^{-4}\;M)$ and McN-A-343 $(10^{-4}\;M).$ However, lower dose of DX did not affect CA secretion by high $K^+\;(5.6{\times}10^{-2}\;M),$ but its higher doses depressed time-dependently CA secretion evoked by high $K^+.$ DX itself did also fail to affect basal CA output. In adrenal glands loaded with DX $(3{\times}10^{-7}\;M),$ CA secretory responses evoked by Bay-K-8644, an activator of L-type $Ca^{2+}$ channels and cyclopiazonic acid, an inhibitor of cytoplasmic $Ca^{2+}-ATPase$ were time-dependently inhibited. Furthermore, daunorubicin $(3{\times}10^{-7}\;M),$ given into the adrenal gland for 60 min, attenuated CA secretory responses evoked by ACh, high $K^+,$ DMPP and McN-A-343. Taken together, these results suggest that DX causes relatively dose- and time-dependent inhibition of CA secretory responses evoked by stimulation of cholinergic (both nicotinic and muscarinic) receptors from the isolated perfused rat adrenal gland. However, lower dose of DX did not affect CA secretion by high $K^+,$ and higher doses of DX reduced time-dependently CA secretion of high $K^+.$ It is thought that these effects of DX may be mediated by inhibiting both influx of extracellular calcium into the rat adrenomedullary chromaffin cells and intracelluar calcium release from the cytoplasmic store. Also, there was no difference in the mode of action between DX and daunorubicin in rat adrenomedullary CA secretion.

• Biomolecules & Therapeutics
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• v.16 no.2
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• pp.147-160
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• 2008

The present study was designed to examine effects of polyphenolic compounds isolated from red wine (PCRW) on the release of catecholamines (CA) from the isolated perfused model of the rat adrenal medulla, and to clarify its mechanism of action. PCRW (20${\sim}$180 ${\mu}$g/mL), given into an adrenal vein for 90 min, caused inhibition of the CA secretory responses evoked by ACh (5.32 mM), high $K^+$ (a direct membrane-depolarizer, 56 mM), DMPP (a selective neuronal nicotinic $N_N$ receptor agonist, 100 ${\mu}$M) and McN-A-343 (a selective muscarinic $M_1$ receptor agonist, 100 ${\mu}$M) in dose- and time-dependent fashion. PCRW itself did not affect basal CA secretion (data not shown). Following the perfusion of PCRW (60 ${\mu}$g/mL), the secretory responses of CA evoked by Bay-K-8644 (a L-type dihydropyridine $Ca^{2+}$ channel activator, 10 ${\mu}$M), cyclopiazonic acid (a cytoplasmic $Ca^{2+}$-ATPase inhibitor, 10 ${\mu}$M) and veratridine (an activator of voltage-dependent $Na^+$ channels, 10 ${\mu}$M) were also markedly blocked, respectively. Interestingly, in the simultaneous presence of PCRW (60 ${\mu}$g/mL) and L-NAME (a selective inhibitor of NO synthase, 30 ${\mu}$M), the inhibitory responses of PCRW on the CA secretion evoked by ACh, high $K^+$, DMPP, McN-A-343, Bay-K-8644 and cyclpiazonic acid were recovered to considerable level of the corresponding control release compared with those effects of PCRW-treatment alone. Practically, the amount of NO released from adrenal medulla after loading of PCRW (180 ${\mu}$g/mL) was significantly increased in comparison to the corresponding basal released level. Collectively, these results obtained here demonstrate that PCRW inhibits the CA secretory responses evoked by stimulation of cholinergic (both muscarinic and nicotinic) receptors as well as by direct membrane-depolarization from the isolated perfused adrenal gland of the normotensive rats. It seems that this inhibitory effect of PCRW is mediated by blocking the influx of both ions through $Na^+$ and $Ca^+{2$} channels into the rat adrenomedullary chromaffin cells as well as by inhibiting the release of $Ca^{2+}$ from the cytoplasmic calcium store, which are due at least partly to the increased NO production through the activation of nitric oxide synthase. Based on these data, it is also thought that PCRW may be beneficial to prevent or alleviate the cardiovascular diseases, such as hypertension and angina pectoris.

• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.6
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• pp.1622-1628
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• 2005

This study was undertaken to define the effect of SoPung-Tang extract on hypertension in spontaneous hypertensive rat and norepinephrine- induced arterial contraction in rabbit. In order to investigate the effect of SoPung-Tang extract on contracted rabbit carotid arterial strips, transverse strips with intact or damaged endothelium were used for the experiment using organ bath. To analyze the mechanism of SoPung-Tang extract-induced relaxation, SoPung-Tang extract infused into contracted arterial strips induced by norepinephrine after treatment of indomethacin, Nu-nitro-L-arginine, methylene blue or tetraethylammonium chloride. Blood pressure was significantly decreased five days after administration of SoPung-Tang extract. SoPung-Tang extract relax arterial strip with endothelium contracted by norepinephrine, but in the strips without endothelium, SoPung-Tang extract- induced relaxation was significantly inhibited. SoPung-Tang relax arterial strip contracted by norepinephrine, but in the strips contracted by high $K^+$, SoPung-Tang extract-induced relaxation was significantly inhibited. The endothelium-dependent relaxation induced by SoPung-Tang extract was decreased by the pre-treatment of $N{\omega}$-nitro-L-arginine or methylene blue, but it was not observed in the strips pre-treated with indomethacin or tetraethylammonium chloride. When $Ca^{2+}$ was applied, the strips which were contracted by norepinephrine in a $Ca^{2+}$-free solution, arterial contraction was increased. But pre-treatment of SoPung-Tang extract inhibited contractile response to $Ca^{2+}$. We suggest that SoPung-Tang could be applied effectively for hypertension and may suppress influx of extra-cellular $Ca^{2+}$ through the formation of nitric oxide in the vascular endothelial cells.

• Molecules and Cells
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• v.27 no.3
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• pp.307-312
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• 2009

The interstitial cells of Cajal (ICC) are pacemaking cells required for gastrointestinal motility. The possibility of whether DA-9701, a novel prokinetic agent formulated with Pharbitis Semen and Corydalis Tuber, modulates pacemaker activities in the ICC was tested using the whole cell patch clamp technique. DA-9701 produced membrane depolarization and increased tonic inward pacemaker currents in the voltage-clamp mode. The application of flufenamic acid, a non-selective cation channel blocker, but not niflumic acid, abolished the generation of pacemaker currents induced by DA-9701. Pretreatment with a $Ca^{2+}$-free solution and thapsigargin, a $Ca^{2+}$-ATPase inhibitor in the endoplasmic reticulum, abolished the generation of pacemaker currents. In addition, the tonic inward currents were inhibited by U-73122, an active phospholipase C inhibitor, but not by $GDP-{\beta}-S$, which permanently binds G-binding proteins. Furthermore, the protein kinase C inhibitors, chelerythrine and calphostin C, did not block the DA-9701-induced pacemaker currents. These results suggest that DA-9701 might affect gastrointestinal motility by the modulation of pacemaker activity in the ICC, and the activation is associated with the non-selective cationic channels via external $Ca^{2+}$ influx, phospholipase C activation, and $Ca^{2+}$ release from internal storage in a G protein-independent and protein kinase C-independent manner.

• The Korean Journal of Pharmacology
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• v.28 no.1
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• pp.91-102
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• 1992

In $Ca^{++}$ containing media, arachidonic acid markedly stimulated superoxide and $H_2O_2$ generation and activated NADPH oxidase. In $Ca^{++}$ free media, stimulatory action of arachidonic acid on NADPH oxidase was not detected. Arachidonic acid-stimulated respiratory burst was inhibited by EGTA, TMB-8, verapamil, diltiazem, nifedipine, dibucaine, lidocaine, CCCP, 2,4-dinitrophenol, sodium arsenate, chlorpromazine, theophylline, $HgCl_2$, PCMB and PCMBSA but not affected by tetrodotoxin, tetraethylammonium chloride and procaine. EGTA almost completely inhibited release of ${\beta}-glucuronidase$ by arachidonic acid and verapamil, CCCP and theophylline slightly inhibited it, whereas dibucaine did not show any significant effect. Arachidonic acid induced $Ca^{++}$ release from intact neutrophils and it was decreased by TMB-8. Arachidonic acid-induced elevation of intracellular free $Ca^{++}$ level was inhibited by EGTA and CCCP and slightly inhibited by TMB-8. Amount of intracellular free $Ca^{++}$ increased by either arachidonic acid plus verapamil or arachidonic acid plus dibucaine was greater than that by arachidonic acid alone. These results suggest that various changes of biochemical events may be implicated in the functional expression in neutrophils activated by arachidonic acid. Arachidonic acid appears to elevate cytosolic free $Ca^{++}$ level by stimulating $Ca^{++}$ release from intracellular $Ca^{++}$ storage sites. During activation of neutrophils, $Ca^{++}$ influx and efflux may be accomplished, simultaneously.

• Archives of Pharmacal Research
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• v.24 no.2
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• pp.164-170
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• 2001

Glutamate receptors-mediated excitoxicity is believed to play a role in the pathophysiology of neurodegenerative diseases. The present study was performed to evaluate the inhibitory effect of fanschinoline, a bis-benzylisoquinoline alkaloid, which has a characteristic as a $Ca^{2+}$channel blockers on excitatory amino acids (EAAS)-induced neurotoxicity in cultured rat cerebellar granule neuron. Fangchinoline (1 and 5$\mu\textrm{m}$) inhibited glutamate (1 ${m}M$), N-methyl-D-aspartate (NMDA; 1 ${m}M$) and kainate (100$\mu\textrm{m}$)-induced neuronal cell death which was measured by trypan blue exclusion test. Fangchinoline (1 and 5$\mu\textrm{m}$) inhibited glutamate release into medium induced by NMDA (1 ${m}M$) and kainate (100$\mu\textrm{m}$), which was measured by HPLC. And fangchinoline (5$\mu\textrm{m}$) inhibited glutamate (1 ${m}M$)-induced elevation of intracellular calcium concentration. These results suggest that inhibition of $Ca^{2+}$influx by fangchinoline may contribute to the beneficial effects on neurodegenerative effect of glutamate in pathophysiological conditions.