• Archives of Pharmacal Research
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• v.26 no.9
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• pp.747-755
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• 2003

The aim of the present study was to clarify whether cotinine affects the release of catecholamines (CA) from the isolated perfused rat adrenal gland, and to establish the mechanism of its action, in comparison with the response of nicotine. Cotinine (0.3∼3 mM), when perfused into an adrenal vein for 60 min, inhibited CA secretory responses evoked by ACh (5.32 mM), DMPP (a selective neuronal nicotinic agonist, 100 $\mu$M for 2 min) and McN-A-343 (a selective muscarinic $M_1 -agonist, 100 \mu$ M for 2 min) in dose- and time-dependent manners. However, cotinine did not affect CA secretion by high $K^+$ (56 mM). Cotinine itself also failed to affect basal CA output. Furthermore, in the presence of cotinine (1 mM), CA secretory responses evoked by Bay-K-8644 (an activator of L-type $Ca^{2+}$ channels, 10 $\mu$ M) and cyclopiazonic acid (an inhibitor of cytoplasmic $Ca^{2+}-ATPase, 10 \mu$ M) were relative time-dependently attenuated. However, nicotine (30$\mu$ M), given into the adrenal gland for 60 min, initially rather enhanced CA secretory responses evoked by ACh and high $K^+$, followed by the inhibition later, while it time-dependently depressed the CA release evoked by McN-A-343 and DMPP. Taken together, these results suggest that cotinine inhibits greatly CA secretion evoked by stimulation of cholinergic (both nicotinic and muscarinic) receptors, but does fail to affect that by the direct membrane-depolarization. It seems that this inhibitory effect of cotinine may be exerted by the cholinergic blockade, which is associated with blocking both the calcium influx into the rat adrenal medullary chromaffin cells and $Ca^{2+}$ release from the cytoplasmic calcium store. It also seems that there is a big difference in the mode of action between cotinine and nicotine in the rat adrenomedullary CA secretion.

• The Korean Journal of Physiology and Pharmacology
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• v.8 no.2
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• pp.101-110
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• 2004

Voltage-sensitive release mechanism was pharmacologically dissected from the $Ca^{2+}-induced\;Ca^{2+}\;release$ in the SR $Ca^{2+}$ release in the rat ventricular myocytes patch-clamped in a whole-cell mode. SR $Ca^{2+}$ release process was monitored by using forward-mode $Na^+-Ca^{2+}$ exchange after restriction of the interactions between $Ca^{2+}$ from SR and $Na^+-Ca^{2+}$ exchange within micro-domains with heavy cytosolic $Ca^{2+}$ buffering with 10 mM BAPTA. During stimulation every 10 s with a pulse roughly mimicking action potential, the initial outward current gradually turned into a huge inward current of $-12.9{\pm}0.5\;pA/pF$. From the inward current, two different inward $I_{NCX}s$ were identified. One was $10\;{\mu}M$ ryanodine-sensitive, constituting $14.2{\pm}2.3%$. It was completely blocked by $CdCl_2$ (0.1 mM and 0.5 mM) and by $Na^+-depletion$. The other was identified by 5 mM $NiCl_2$ after suppression of $I_{CaL}$ and ryanodine receptor, constituting $14.8{\pm}1.6%$. This latter was blocked by either 10 mM caffeine-induced SR $Ca^{2+}-depletion$ or 1 mM tetracaine. IV-relationships illustrated that the latter was activated until the peak in $30{\sim}35\;mV$ lower voltages than the former. Overall, it was concluded that the SR $Ca^{2+}$ release process in the rat ventricular myocytes is mediated by the voltage-sensitive release mechanism in addition to the $Ca^{2+}-induced-Ca^{2+}\;release$.

• The Korean Journal of Physiology and Pharmacology
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• v.23 no.5
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• pp.345-356
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• 2019

Docosahexaenoic acid (DHA), an omega-3-fatty acid, modulates multiple cellular functions. In this study, we addressed the effects of DHA on human umbilical vein endothelial cell calcium transient and endothelial nitric oxide synthase (eNOS) phosphorylation under control and adenosine triphosphate (ATP, $100{\mu}M$) stimulated conditions. Cells were treated for 48 h with DHA concentrations from 3 to $50{\mu}M$. Calcium transient was measured using the fluorescent dye Fura-2-AM and eNOS phosphorylation was addressed by western blot. DHA dose-dependently reduced the ATP stimulated $Ca^{2+}$-transient. This effect was preserved in the presence of BAPTA (10 and $20{\mu}M$) which chelated the intracellular calcium, but eliminated after withdrawal of extracellular calcium, application of 2-aminoethoxy-diphenylborane ($75{\mu}M$) to inhibit store-operated calcium channel or thapsigargin ($2{\mu}M$) to delete calcium store. In addition, DHA ($12{\mu}M$) increased ser1177/thr495 phosphorylation of eNOS under baseline conditions but had no significant effect on this ratio under conditions of ATP stimulation. In conclusion, DHA dose-dependently inhibited the ATP-induced calcium transient, probably via store-operated calcium channels. Furthermore, DHA changed eNOS phosphorylation suggesting activation of the enzyme. Hence, DHA may shift the regulation of eNOS away from a $Ca^{2+}$ activated mode to a preferentially controlled phosphorylation mode.

• Asian-Australasian Journal of Animal Sciences
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• v.16 no.11
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• pp.1690-1694
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• 2003

The large and rapid changes of glucose utilization in lactating mammary tissue in response to changes in nutritional state must be largely related by external signal of insulin. This also must be related with the quantity and composition of the diet in vivo. To characterize the mode of growth factors and gut regulatory peptides with insulin, in vitro experiment was conducted with HC11 cells. All the growth factor alone and the combinations of growth factors significantly (p<0.05) increased in glucose uptake. Insulin, EGF and IGF-1 exhibited a stimulation of glucose uptake for at least 24 h. Furthermore, the highest (p<0.05) synergistic effect was shown in EGF plus IGF-1 and the second synergistic effect in insulin plus EGF while no synergistic effect was found between insulin and IGF-1. However, the gut regulatory peptides neither potentiated nor inhibited the action of insulin on glucose uptake. Although growth factors did not modulates glucose uptake via increasing the rate of translation of the GLUT1 protein, RT-PCR analysis indicated that the growth factors significantly (p<0.05) increased the expression of GLUT1. The growth factors are therefore shown to be capable of modulating glucose uptake by transcription level with insulin in HC 11 cells.

• Biomolecules & Therapeutics
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• v.11 no.1
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• pp.33-40
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• 2003

The present study was designed to investigate the effects of green tea extract (CUMC6335) and epigallocatechin gallate (EGCG) on secretion of catecholamines (CA) in the isolated perfused rat adrenal gland. ill the presence of CUMC6335 (100 $\mu\textrm{g}$/mL) into an adrenal vein for 60 min, CA secretory responses evoked by ACh(5.32 mM), high $K^+$ (56 mM) and Bay-K-8644 (10$\mu$M for 4 min) from the isolated perfused rat adrenal glands were greatly inhibited in a time-dependent fashion. However, EGCG (8 $\mu\textrm{g}$/mL) did not affect CA release evoked by ACh, high $K^+$ and Bay-K-8644. CUMC6335 itself did fail to affect basal catecholamine output. Taken together, these results demonstrate that CUMC6335 inhibits greatly CA secretion evoked by stimulation of cholinergic nicotinic receptors as well as by the direct membrane deplarization from the isolated perfused rat adrenal gland. It is felt that this inhibitory effect of CUMC6335 may be due to blocking action of the L-type dihydropyridine calcium channels in the rat adrenal medullary chromaffin cells, which is relevant to the cholinergic nicotinic blockade. It seems that there is a big difference in mode of action between CUMC6335 and EGCG.

• Asian-Australasian Journal of Animal Sciences
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• v.8 no.6
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• pp.533-555
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• 1995

Direct-fed microbials (DFM) have been used to enhance milk production in lactating cattle and to increase feed efficiency and body weight gain in growing ruminants. Primary microorganisms that have been used as DFM for ruminants are fungal cultures including Aspergillus oryzae and Saccharomyces cerevisiae and lactic acid bacteria such as Lactobacillus or Streptococcus. Attempts have been made to determine the basic mechanisms describing beneficial effects of DFM supplements. Various modes of action for DFM have been suggested including : stimulation of ruminal microbial growth, stabilization of ruminal pH, changes in ruminal microbial fermentation pattern, increases in digestibility of nutrients ingested, greater nutrient flow to the small intestine, greater nutrient retention and alleviation of stress, however, these responses have not been observed consistently. Variations in microbial supplements, dosage level, production level and age of the animal, diet and environmental condition or various combinations of the above may partially explain the inconsistencies in response. This review summarizes production responses that have been observed under various conditions with supplemental DFM and also corresponding modification of ruminal fermentation and other changes in the gastrointestinal tract of ruminant animals.

• Asian-Australasian Journal of Animal Sciences
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• v.18 no.7
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• pp.1048-1060
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• 2005

Dietary acidifiers appear to be a possible alternative to feed antibiotics in order to improve performance of weaning pigs. It is generally known that dietary acidifiers lower gastric pH, resulting in increased activity of proteolytic enzymes, improved protein digestibility and inhibiting the proliferation of pathogenic bacteria in GI tract. It is also hypothesized that acidifiers could be related to reduction of gastric emptying rate, energy source in intestine, chelation of minerals, stimulation of digestive enzymes and intermediate metabolism. However, the exact mode of action still remains questionable. Organic acidifiers have been widely used for weaning pigs' diets for decades and most common organic acidifiers contain fumaric, citric, formic and/or lactic acid. Many researchers have observed that dietary acidifier supplementation improved growth performance and health status in weaning pigs. Recently inorganic acidifiers as well as organic acidifiers have drawn much attention due to improving performance of weaning pigs with a low cost. Several researchers introduced the use of salt form of acidifiers because of convenient application and better effects than pure state acids. However, considerable variations in results of acidifier supplementation have been reported in response of weaning pigs. The inconsistent responses to dietary acidifiers could be explained by feed palatability, sources and composition of diet, supplementation level of acidifier and age of animals.

• Archives of Pharmacal Research
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• v.28 no.8
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• pp.914-922
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• 2005

The present study was designed to examine the effects of green tea extract (CUMC6335) and epigallocatechin gallate (EGCG) on secretion of catecholamines (CA) in the isolated perfused rabbit adrenal gland. In the presence of CUMC6335 $(200 {\mu}g/mL)$ into an adrenal vein for 60min, CA secretory responses evoked by ACh (5.32 mM), high $K^+$ (56 mM), DMPP $(100{\mu}M \;for\;2min)$, and Bay-K-8644 $(10{\mu}M\;for\;4min)$ from the isolated perfused rabbit adrenal glands were greatly inhibited in a time-dependent fashion. However, EGCG $(10{\mu}g/mL)$ did not affect CA release evoked by ACh, high $K^+$, and Bay-K-8644. CUMC6335 itself failed to affect basal catecholamine output. Taken together, these results demonstrate that CUMC6335 inhibits CA secretion evoked by stimulation of cholinergic nicotinic receptors, as well as the direct membrane depolarization from the isolated perfused rabbit adrenal gland. It is thought that this inhibitory effect of CUMC6335 may be due at least in part to the blocking action of the L-type dihydropyridine calcium channels in the rabbit adrenomedullary chromaffin cells, which is relevant to the cholinergic nicotinic blockade. It seems that there is a big difference in mode of action between CUMC6335 and EGCG.

• Speech Sciences
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• v.14 no.2
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• pp.35-42
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• 2007

The aim of this study is to analyze the correlation between current intensity and amplitude of stimulus artifact on the cochlear implantee, and to find out basic information to check the device failure. Subjects were a prelingual child and 3 postlingual adults with more than severe hearing losses. The charge-balanced biphasic pulses were presented at stimulus rates of 11 pulses per second, each pulse width of $25{\mu}s$ with monopolar mode(MP1+2). Current intensities were delivered at 27.5, 33.7, 41.3, 50.5, 61.9, $75.8{\mu}A$. Stimulus artifacts were recorded by evoked potential system. This procedure was performed just before the initial stimulation, and then, the amplitude of stimulus artifacts were compared with each current intensity. The amplitude of stimulus artifacts was increased significantly according to the current intensity (p<0.01). The results suggest that the change of the amplitude of stimulus artifact can be used as a good cue to check the device failure in the cochlear implantee.

• The Korean Journal of Physiology and Pharmacology
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• v.6 no.6
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• pp.305-309
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• 2002

There are some evidences that $K^+$ efflux evoked by muscarinic stimulation is not mainly mediated by large conductance $K^+$ (BK) channels in salivary gland. In this experiment, we therefore characterised non BK channels in rat submandibular gland acinar cells and examined the possibility of agonist effect on this channel using a patch clamp technique. Two types of $K^+$ channels were observed in these cells. BK channels were observed in 3 cells from total 6 cells and its average conductance was $152{\pm}7$ pS (n=3). The conductance of the another types of $K^+$ channel was estimated as $71{\pm}7$ pS (n=6). On the basis of the conductance of this channel, we defined this channel as intermediate conductance $K^+$ (IK) channels, which were observed from all 6 cells we studied. When we increased $Ca^{2+}$ concentration of the bath solution in inside-out mode, the IK channel activity was greatly increased, suggesting this channel is $Ca^{2+}$ sensitive. We next examined the effect of carbachol (CCh) and isoproterenol on the activity of the IK channels. $10^{-5}$ M isoproterenol significantly increased the open probability (Po) from $0.08{\pm}0.02$ to $0.21{\pm}0.03$ (n=4, P<0.05). Application of $10^{-5}$ M CCh also increased Po from $0.048{\pm}0.03$ to $0.55{\pm}0.33$ (n=5, P<0.05) at the maximum channel activity. The degree of BK channel activation induced by the same concentration of CCh was lower than that of IK channels; Po value was $0.011{\pm}0.003$ and $0.027{\pm}0.005$ in control and during CCh stimulation (n=3), respectively. The result suggests that IK channels exist in salivary acinar cells and its channel activity is regulated by muscaricinic and ${\beta}-adrenergic$ agonist. We conclude that IK channels also play a putative role in secretion as well as the BK channels in rat submandibular gland acinar cells.