• The Korean Journal of Physiology
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• v.24 no.2
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• pp.293-303
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• 1990

The contractile action of barium $(Ba^{2+})$ was investigated in the arterial strip of rabbit renal artery. The helical strip of isolated renal artery was immersed in the Tris-buffered Tyrode's solution equilibrated with 100% $O_2$ at $37^{\circ}C$ and its isometric tension was measured. $Ba^{2+}-induced$ contraction of arterial strip was dose-dependent and its maximal tension corresponded to $92.1{\pm}4.5%$ of tension by $K^+(100\;mM)$. $Ba^{2+}-induced$ contraction did not show the tachyphylactic phenomenon in the normal Tyrode's solution. $Ba^{2+}$ induced the tonic contraction in the $Ca^{2+}-free$ tyrode's solution and that was increased by the extracellula addition of $Ca^{2+}$. During the repeated exposure of the same dose of $Ba^{2+}\;(10\;mM)$ in the $Ca^{2+}-free$ Tyrode's solution, $Ba^{2+}-induced$ contraction was progressively decreased. Even though the intracellular NE-and caffeine-sensitive $Ca^{2+}$ was depleted, $Ba^{2+}$ induced the tonic contraction. After the pretreatment of lanthnum or verapamil, $Ba^{2+}$ did not induce contraction. $Ba^{2+}-induced$contraction was suppressed by extracellular $K^+$ in the normal Tyrode's solution and that was dependent on $K^+$ concentration. Suppressive effect of $K^+\;(14\;mM)$ on the $Ba^{2+}-induced$ contraction was also dependent on the intracellular $Ca^{2+}$ concentration. From the above resuts, it is suggested that $Ba^{2+}$ activate indirectly the contractile process by promoting the mobilization of intracellular $Ca^{2+}$ and the influx of extracellular $Ca^{2+}$. It is also suggested that action of $Ba^{2+}$ on the $Ca^{2+}-activated$ $K^+$ channel can result in the depolarization of cell membrane in the rabbit renal artery.

• Biomedical Science Letters
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• v.10 no.1
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• pp.1-8
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• 2004

Cordycepin separated from Cordyceps militaris is a major physiologic active component in Cordyceps militaris. The platelet aggregation is stimulated by $Ca^{2+}$, which is either mobilized from intracellular endoplasmic reticulum or transported from extracellular space. cGMP antagonizes the actions of $Ca^{2+}$. Based on these facts, we have investigated the effects of cordycepin on the mobilization of $Ca^{2+}$ and the production of cGMP on collagen ($10\mu$g/ml)-induced human platelet aggregation. Cordycepin potently stimulated the human platelet aggregation induced by collagen ($10\mu$g/ml) in a dose-dependent manner. Cordycepin (500 $\mu$M) inhibited also the collagen-induced human platelet aggregation in the presence both 1 mM and 2 mM of $CaCl_2$. These are in accord with the results that cordycepin inhibited the $Ca^{2+}$- influx on collagen-induced human platelet aggregation. These results suggest that cordycepin decrease the intracellular $Ca^{2+}$ concentration to inhibit collagen-induced human platelet aggregation. Besides, cordycepin increased the level of cGMP on collagen-induced human platelet aggregation. This result is related with the decrease of intracellular $Ca^{2+}$ concentration, because cGMP inhibits the mobilization of $Ca^{2+}$. In addition, cordycepin inhibited the human platelet aggregation induced by LY -83583, inhibitor of guanylate cyclase. This result suggested that cordycepin inhibit the platelet aggregation by stimulating the activity of guanylate cyclase. In conclusion, we demonstrated that cordycepin might have the antiplatelet function by inhibiting $Ca^{2+}$-mobilization via the stimulation of the production of cGMP.

• The Korean Journal of Physiology and Pharmacology
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• v.3 no.4
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• pp.439-445
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• 1999

This study is to investigate the mechanism of inhibitory effect of imipramine on the calcium utilization in single cells isolated from canine detrusor. 2 mm thick smooth muscle chops were incubated in 0.12% collagenase solution at $36^{circ}C,$ and aerated with 95% $O_2/5%\;CO_2,$ and then cell suspension was examined. Acetylcholine (ACh) evoked a concentration-dependent contraction of the isolated detrusor cells in normal physiologic salt solution (PSS), and the ACh-induced contraction was significantly inhibited by imipramine. In $Ca^{2+}-free$ PSS, ACh-induced contraction was less than those in normal PSS and it was not affected by the pretreatment with imipramine. $Ca^{2+}-induced$ contraction in $Ca^{2+}-free$ PSS was supressed by imipramine, but addition of A 23187, a calcium ionophore, overcomed the inhibitory effect of imipramine. High potassium-depolarization (40 mM KCl) evoked cell contraction, which was inhibited by imipramine. Caffeine, a releasing agent of the stored $Ca^{2+}$ from sarcoplasmic reticulum, evoked a contraction of the cells that was not blocked by the pretreatment with imipramine. These results suggest that imipramine inhibits the influx of calcium in the detrusor cells through both the receptor-operated- and voltage-gated-calcium channels, but does not affect the release of calcium from intracellular storage site.

• Journal of fish pathology
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• v.9 no.1
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• pp.41-51
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• 1996

The present study was undertaken to investigate the physiological characteristics of the adrenergic responses in the tilapia dorsal aorta. Epinephrine, norepinephrine, clonidine and methoxamine in the presence of propranolol($3{\times}10^{-6}$M), induced only endothelium-independent and concentration-dependent vasocontractions in tilapia dorsal aorta. The rank order of potency of adrenergic agonists inducing vasocontraction was epinephrine>norepinephrine>phenylephrine>clonidine>ethoxamine, Yohimbine produced a parallel shift of the concentration-vascontraction curves of epinephrine, norepinephrine, phenylephrine and clonidine to the right, while prazosin depressed the maximum responses of epinephrine and norepinephrine. Calcium-free physiological solution and verapamil markedly reduced epinephrine or norepinephrine-induced vasocontractions. These results suggest that a-adrenergic agonists produce only on endothelium-inedpenent casoconstrictions in tilapia dorsal aorta and these effect of a-adrenergic agonists, which might be associated with both calcium release from intracellular stores and calcium influx through voltage-dependent calcium channel.

• Natural Product Sciences
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• v.19 no.1
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• pp.36-48
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• 2013

The aim of the present study was to investigate the effects of several fractions obtained from methylene chloride ($CH_2Cl_2$) extract of self-fermented pine needle (SFPNE) on the acetylcholine (ACh)-evoked CA release from the isolated perfused model of the rat adrenal medulla and to establish the mechanism of the most active fraction (Fr.)-induced inhibitory action on the CA release. We obtained 6 fractions from $CH_2Cl_2$ extract of self-fermented pine needle. For the ACh (5.32 mM)-evoked CA release, the following rank order of inhibitory potency was obtained: Fr.4-5 > Fr.8-11 ${\gg}$ Fr.3 > Fr.6 = Fr.7 > Fr.1-2. Fr. 4 - 5 (60 ${\mu}g/mL$) perfused into an adrenal vein for 90 min produced relatively time-dependent inhibition of the CA secretory responses to ACh (5.32 mM), DMPP (100 ${\mu}M$), McN-A-343 (100 ${\mu}M$) and high $K^+$ (56 mM). Fr. 4 - 5 itself did not affect basal CA secretion. Also, in the presence of Fr. 4 - 5 (60 ${\mu}g/mL$), the CA secretory responses to angiotensin II (AngII, 0.1 ${\mu}M$), veratridine (50 ${\mu}M$), Bay-K-8644 (10 ${\mu}M$), and cyclopiazonic acid (10 ${\mu}M$) were significantly reduced, respectively. In the simultaneous presence of Fr. 4 - 5 (60 ${\mu}g/mL$) and L-NAME (30 ${\mu}M$), the inhibitory responses of Fr. 4 - 5 on the CA secretion evoked by ACh, DMPP, high $K^+$, AngII, Bay-K-8644 and veratridine were considerably recovered to the extent of the corresponding control secretion compared with that of Fr. 4 - 5-treatment alone. The level of NO released from adrenal medulla after the treatment of Fr. 4 - 5 (60 ${\mu}g/mL$) was greatly elevated compared with the basal level. Taken together, these results demonstrate that Fr. 4 - 5 inhibits the CA secretion from the isolated perfused rat adrenal medulla evoked by stimulation of cholinergic receptors as well as by direct membrane-depolarization. It seems that this inhibitory effect of Fr. 4 - 5 is mediated by blocking the influx of $Ca^{2+}$ and $Na^+$ into the adrenomedullary chromaffin cells as well as by inhibition of $Ca^{2+}$ release from the cytoplasmic calcium store, which is evoked at least partly through the increased NO production due to the activation of NO synthase. Based on these results, it is also thought that Fr. 4 - 5 isolated from $CH_2Cl_2$ extract of pine needle may contain beneficial antihypertensive components to prevent or treat hypertension.

• Natural Product Sciences
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• v.19 no.4
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• pp.290-296
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• 2013

In preliminary tests, we examined the effect of several fractions isolated from fermented pine needle extract on pacemaker potentials in cultured interstitial cells of Cajal (ICCs) from the mouse colon using a whole cell patch clamp technique. Among these fractions, Fraction 3 (F3) elicited the most powerful depolarization of membrane. Therefore, the aim of the present study was to investigate the effect of F3 obtained from fermented extract of Pinus densiflora needle on pacemaker potentials in ICCs and to establish its mechanism of action. Colonic ICCs generated spontaneous periodic pacemaker potentials in the current-clamp mode. F3 depolarized the membrane and decreased the frequency and amplitude of pacemaker potentials in a dose-dependent fashion. The F3-induced effects on pacemaker potentials were blocked by methoctramine, a muscarinic $M_2$ receptor antagonist, and by glycopyrrolate, a muscarinic $M_3$ receptor antagonist. The F3-induced effects on pacemaker potentials were blocked by external $Na^+$-free solution and by flufenamic acid, a non-selective cation channel blocker, as well as by the removal of external $Ca^{2+}$ and in the presence of thapsigargin, a $Ca^{2+}$-ATPase inhibitor in the endoplasmic reticulum. Taken together, these results suggest that F3 of pine needle extract modulates the pacemaker activity of colonic ICCs by the activation of non-selective cation channels via muscarinic $M_2$ and $M_3$ receptors. And external $Ca^{2+}$ influx and intracellular $Ca^{2+}$ release are involved in F3 actions on ICCs.

• Proceedings of the Ginseng society Conference
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• 1993.09a
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• pp.94-101
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• 1993

Lipophilic fraction(LF) from Panax ginseng C.A. Meyer inhibited the aggregation of human platelets induced by th rombin(0.1u/$m{\ell}$). LF and Molsidomine(vasodilator) induced the stimulation of cGMP - elevation and 50KD - Phosphorylation. and then the inhibition of 20KD - Phosphorylation in human platelets activated by thrombin. LF also inhibited the $Ca^{2-}-influx$ into platelets. When rat(SD : male) was fed with LF, the level of cGMP was increased in rat platelets stimulated by collagen and thrombin. On the other hand. verapamil, $Ca^{2-}-antagonist$ increased cAMP level ;n platelet stimulated by thrombin. but LF does not affected. However LF potently inhibited the thromboxane $A_2(TXA_2)$ production. The results suggest that the inhibitory effects of LF are mediated by regulation the phosphorylatior. of 50KD via cGMP-elevation and depend upon the decrease of $TXA_2$ level.

• The Korean Journal of Physiology and Pharmacology
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• v.7 no.4
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• pp.231-238
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• 2003

The present study was undertaken to investigate the effect of bradykinin on secretion of catecholamines (CA) evoked by stimulation of cholinergic receptors and membrane depolarization from the isolated perfused model of the rat adrenal glands, and to elucidate its mechanism of action. Bradykinin $(3{\times}10^{-8}M)$ alone produced a weak secretory response of the CA. however, the perfusion with bradykinin $(3{\times}10^{-8}M)$ into an adrenal vein of the rat adrenal gland for 90 min enhanced markedly the secretory responses of CA evoked by ACh $(5.32{\times}10^{-3}M)$, excess $K^+$ ($5.6{\times}10^{-2}M$, a membrane depolarizer), DMPP ($10^{-4}$ M, a selective neuronal nicotinic agonist) and McN-A-343 ($10^{-4}$ M, a selective M1-muscarinic agonist). Moreover, bradykinin ($3{\times}10^{-8}$ M) in to an adrenal vein for 90 min also augmented the CA release evoked by BAY-K-8644, an activator of the dihydropyridine L-type $Ca^{2+}$ channels. However, in the presence of $(N-Methyl-D-Phe^7)$-bradykinin trifluoroacetate salt $(3{\times}10^{-8}M)$, an antagonist of $BK_2$-bradykinin receptor, bradykinin no longer enhanced the CA secretion evoked by Ach and high potassium whereas the pretreatment with Lys-$(des-Arg^9,\;Leu^9)$-bradykinin trifluoroacetate salt $(3{\times}10^{-8}M)$, an antagonist of $BK_1$-bradykinin receptor did fail to affect them. Furthermore, the perfusion with bradykinin $(3{\times}10^{-6}M)$ into an adrenal vein of the rabbit adrenal gland for 90 min enhanced markedly the secretory responses of CA evoked by excess $K^+$ $(5.6{\times}10^{-2}M)$. Collectively, these experimental results suggest that bradykinin enhances the CA secretion from the rat adrenal medulla evoked by cholinergic stimulation (both nicotininc and muscarinic receptors) and membrane depolarization through the activation of $B_2$-bradykinin receptors, not through $B_1$-bradykinin receptors. This facilitatory effect of bradykinin seems to be associated to the increased $Ca^{2+}$ influx through the activation of the dihydropyridine L-type $Ca^{2+}$ channels.

• Nutrition Research and Practice
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• v.8 no.2
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• pp.146-150
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• 2014

BACKGROUND/OBJECTIVES: Cholecystokinin (CCK), a hormone or neuropeptide, is secreted in response to intraluminal nutrients by enteroendocrine I-cells of the intestine and has important physiological actions related to appetite regulation and satiety. The stimulation on CCK secretion from the intestine is of potential relevance for body weight management. Naringenin (4',5,7-trihydroxyflavanone) and its glycoside naringin (naringenin 7-rhamnoglucoside) have been reported to have many biological functions. In the current study, we investigated the question of whether naringenin and naringin could stimulate CCK secretion and then examined the mechanisms involved in CCK release. MATERIALS/METHODS: STC-1 cells were used as a model of enteroendocrine cells. CCK release and changes in intracellular $Ca^{2+}$ ($[Ca^{2+}]_i$) were measured after incubation of cells with naringenin and naringin for 1 h. RESULTS: Naringenin caused significant (P < 0.05) stimulation of CCK secretion, but naringin did not. In addition, regarding the secretory mechanisms, naringenin-induced CCK secretion involved increases in $[Ca^{2+}]_i$, influx of extracellular $Ca^{2+}$, at least in part, and activation of TRP channels, including TRPA1. CONCLUSION: Findings of this study suggest that naringenin could have a role in appetite regulation and satiety.

• Korean Journal of Oriental Medicine
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• v.10 no.2
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• pp.79-92
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• 2004

Objectives : This experiments were performed to determine the effect of OYakSoonGi-San extract on hypertension in spontaneous hypertensive rat and norepinephrine-induced arterial contraction in rabbit. Methods : In order to define the effect of OYakSoonGi-San 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 OYakSoonGi-San extract-induced relaxation, OYakSoonGi-San extract infused into contracted arterial strips induced by norepinephrine after treatment of indomethacin, $N{\omega}-nitro-L-arginine$, methylene blue or tetraethylammonium chloride. Results : Blood pressure was significantly decreased five days after administration of OYakSoonGi-San extract. The relaxation effect of OYakSoonGi-San extract was dependent on the presence of endothelium, showing that OYakSoonGi-San extract-induced relaxation was not observed in the strips without endothelium. Also OYakSoonGi-San extract-induced relaxation was significantly inhibited in arterial strips which were contracted by high $K^+$. OYakSoonGi-San extract-indeced relaxation was significantly inhibited 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 additive application of $Ca^{2+}$ in arterial strips which were pre-contracted by norepinephrine in a $Ca^{2+}$-free solution, arterial contraction was increased. But contractile response to $Ca^{2+}$ was attenuated by pre-treatment of OYakSoonGi-San extract. Conclusions : These results demonstrated that OYakSoonGi-San could be applied effectively to hypertension and may inhibit agonist-induced contraction through an decrease influx of extra-cellular $Ca^{2+}$ by the formation of nitric oxide in the vascular endothelial cells.