• Proceedings of the Zoological Society Korea Conference
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• 1999.10b
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• pp.176.1-176
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• 1999

No Abstract, See Full Text

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.75.2-75.2
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• 2003

The present study was designed to compare the effects of conotoxin GVIA, a selective blocker of N-type voltage-dependent calcium channels (VDCC) and cilnidipine, a blocker of both L- and N-type VDCC, on the secretion of catecholamines (CA) evoked by cholinergic stimulation and membrane-depolarization in the isolated perfused rat adrenal gland, and also to establish the mechanism of action. 1. The inhibition of the CA secretory response evoked by acetylcholine (5.32 x 10$\^$-3/ ${\mu}$M) was stronger in cilnidipine-treated glands than in conotoxin GVIA-treated glands. (omitted)

• The Korean Journal of Physiology and Pharmacology
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• v.15 no.5
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• pp.285-289
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• 2011

Shilajit, a medicine herb commonly used in Ayurveda, has been reported to contain at least 85 minerals in ionic form that act on a variety of chemical, biological, and physical stressors. The substantia gelatinosa (SG) neurons of the trigeminal subnucleus caudalis (Vc) are involved in orofacial nociceptive processing. Shilajit has been reported to be an injury and muscular pain reliever but there have been few functional studies of the effect of Shilajit on the SG neurons of the Vc. Therefore, whole cell and gramicidin-perfotrated patch clamp studies were performed to examine the action mechanism of Shilajit on the SG neurons of Vc from mouse brainstem slices. In the whole cell patch clamp mode, Shilajit induced short-lived and repeatable inward currents under the condition of a high chloride pipette solution on all the SG neurons tested. The Shilajit-induced inward currents were concentration dependent and maintained in the presence of tetrodotoxin (TTX), a voltage gated $Na^+$ channel blocker, CNQX, a non-NMDA glutamate receptor antagonist, and AP5, an NMDA receptor antagonist. The Shilajit-induced responses were partially suppressed by picrotoxin, a $GABA_A$ receptor antagonist, and totally blocked in the presence of strychnine, a glycine receptor antagonist, however not affected by mecamylamine hydrochloride (MCH), a nicotinic acetylcholine receptor antagonist. Under the potassium gluconate pipette solution at holding potential 0 mV, Shilajit induced repeatable outward current. These results show that Shilajit has inhibitory effects on the SG neurons of Vc through chloride ion channels by activation of the glycine receptor and $GABA_A$ receptor, indicating that Shilajit contains sedating ingredients for the central nervous system. These results also suggest that Shilajit may be a potential target for modulating orofacial pain processing.

• The Korean Journal of Pharmacology
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• v.28 no.2
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• pp.171-179
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• 1992

Effects of a $M_1$ receptor antagonist, pirenzepine, a $M_2$ receptor antagonist, AF-DX116, and a nicotinic receptor antagonist, mecamylamine on the pressor responses to preganglionic sympathetic nerve stimulation (PNS) and McN-A-343 and DMPP in spinal (pithed) rabbits were investigated, in order to elucidate a functional role of $M_1$, $M_2$ and nicotinic receptors in ganglionic transmission. Pirenzepine and AF-DX116 selectively inhibited the McN-A-343-induced pressor response in chlorisondamine-treated rabbit and the BCh-induced bradycardia, respectively. Electrical stimulations of preganglionic sympathetic outflow at T8 level produced increases in blood pressure. Pirenzepine $(3\;{\mu}g/kg)$ significantly inhibited the PNS-induced pressor response and the degree of inhibition was not changed by increasing the doses to $100\;{\mu}g/kg$. AF-DX116 $(100\;{\mu}g/kg)$ had no effect on the PNS-induced pressor response. Mecamylamine inhibited the PNS-induced pressor response in a dose-dependent manner. The inhibitory action of mecamylamine was significantly augmented by combined-treatment with pirenzepine $(30\;{\mu}g/kg)$ but AF-DX116 $(100\;{\mu}g/kg)$ did not affect the inhibitory action of mecamylamine. McN-A-343 and DMPP elicited pressor response in the spinal rabbit. Pirenzepine and AF-DX116 dose-dependently inhibited the McN-A-343-induced pressor response but they did not affect DMPP-induced pressor response. Mecamylamine inhibited both pressor responses induced by McN-A-343 and DMPP. These results suggest that not only nicotinic receptors but also $M_1$ receptors play a facilitatory role in ganglionic transmission but $M_2$ receptors do not contribute the transmission in spinal (pithed) rabbits.

• Biomolecules & Therapeutics
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• v.15 no.2
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• pp.108-117
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• 2007

The aim of the present study was to investigate the effect of glibenclamide, a hypoglycemic sulfonylurea, which selectively blocks ATP-sensitive K$^+$ channels, on secretion of catecholamines (CA) evoked by cholinergic stimulation and membrane depolarization from the isolated perfused rat adrenal glands. The perfusion of glibenclamide (1.0 mM) into an adrenal vein for 90 min produced time-dependently enhanced the CA secretory responses evoked by ACh (5.32 mM), high K$^+$ (a direct membrane depolarizer, 56 mM), DMPP (a selective neuronal nicotinic receptor agonist, 100 ${\mu}$M for 2 min), McN-A-343 (a selective muscarinic M1 receptor agonist, 100 ${\mu}$M for 2 min), Bay-K-8644 (an activator of L-type dihydropyridine Ca$^{2+}$ channels, 10 ${\mu}$M for 4 min) and cyclopiazonic acid (an activator of cytoplasmic Ca$^{2+}$-ATPase, 10 ${\mu}$M for 4 min). In adrenal glands simultaneously preloaded with glibenclamide (1.0 mM) and nicorandil (a selective opener of ATP-sensitive K$^+$ channels, 1.0 mM), the CA secretory responses evoked by ACh, high potassium, DMPP, McN-A-343, Bay-K-8644 and cyclopiazonic acid were recovered to the considerable extent of the control release in comparison with that of glibenclamide-treatment only. Taken together, the present study demonstrates that glibenclamide enhances the adrenal CA secretion in response to stimulation of cholinergic (both nicotinic and muscarinic) receptors as well as by membrane depolarization from the isolated perfused rat adrenal glands. It seems that this facilitatory effect of glibenclamide may be mediated by enhancement of both Ca$^{2+}$ influx and the Ca$^{2+}$ release from intracellular store through the blockade of K$_{ATP}$ channels in the rat adrenomedullary chromaffin cells. These results suggest that glibenclamide-sensitive K$_{ATP}$ channels may play a regulatory role in the rat adrenomedullary CA secretion.

• The Korean Journal of Physiology and Pharmacology
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• v.5 no.2
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• pp.189-197
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• 2001

To investigate propofol's effects on ionic currents induced by ${\gamma}-aminobutyric$ acid (GABA) and glycine as well as on those produced by the nicotinic acetylcholine- and glutamate-responsive channels, rat dorsal raphe neurons were acutely dissociated and the nystatin-perforated patch-clamp technique under voltage-clamp conditions was used to observe their responses to the administration of propofol. Propofol evoked ion currents in a dose-dependent manner, and propofol $(10^{-4}\;M)$ was used to elicit ion currents through the activation of $GABA_A,$ glycine, nicotinic acetylcholine and glutamate receptors. Propofol at a clinically relevant concentration $(10^{-5}\;M)$ potentiated $GABA_A-,$ glycine- and NMDA receptor-mediated currents. The potentiating action of propofol on $GABA_A-,$ glycine- and NMDA receptor-mediated responses involved neither opioid receptors nor G-proteins. Apparently, propofol modulates inhibitory and excitatory neurotransmitter-activated ion channels either by acting directly on the receptors or by potentiating the effects of the neurotransmitters, and this modulation appears to be responsible for the majority of the anaesthetic and/or adverse effects.

• The Korean Journal of Physiology and Pharmacology
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• v.9 no.1
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• pp.37-43
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• 2005

Our previous report demonstrated that chick myoblasts are equipped with $Ca^{2+}$-permeable stretchactivated channels and $Ca^{2+}-activated$ potassium channels ($K_{Ca}$), and that hyperpolarization-induced by $K_{Ca}$ channels provides driving force for $Ca^{2+}$ influx through the stretch-activated channels into the cells. Here, we showed that acetylcholine (ACh) also hyperpolarized the membrane of cultured chick myoblasts, suggesting that nicotinic acetylcholine receptor (nAChR) may be another pathway for $Ca^{2+}$ influx. Under cell-attatched patch configuration, ACh increased the open probability of $K_{Ca}$ channels from 0.007 to 0.055 only when extracellular $Ca^{2+}$ was present. Nicotine, a nAChR agonist, increased the open probability of $K_{Ca}$ channels from 0.008 to 0.023, whereas muscarine failed to do so. Since the activity of $K_{Ca}$ channel is sensitive to intracellular $Ca^{2+}$ level, nAChR seems to be capable of inducing $Ca^{2+}$ influx. Using the $Ca^{2+}$ imaging analysis, we were able to provide direct evidence that ACh induced $Ca^{2+}$ influx from extracellular solution, which was dramatically increased by valinomycin-mediated hyperpolarization. In addition, ACh hyperpolarized the membrane potential from $-12.5{\pm}3$ to $-31.2{\pm}5$ mV by generating the outward current through $K_{Ca}$ channels. These results suggest that activation of nAChR increases $Ca^{2+}$ influx, which activates $K_{Ca}$ channels, thereby hyperpolarizing the membrane potential in chick myoblasts.

• The Korean Journal of Physiology and Pharmacology
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• v.19 no.3
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• pp.257-262
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• 2015

It is well known that cigarette smoke can cause erectile dysfunction by affecting the penile vascular system. However, the exact effects of nicotine on the corpus cavernosum remains poorly understood. Nicotine has been reported to cause relaxation of the corpus cavernosum; it has also been reported to cause both contraction and relaxation. Therefore, high concentrations of nicotine were studied in strips from the rabbit corpus cavernosum to better understand its effects. The proximal penile corpus cavernosal strips from male rabbits weighing approximately 4 kg were used in organ bath studies. Nicotine in high concentrations ($10^{-5}{\sim}10^{-4}M$) produced dose-dependent contractions of the corpus cavernosal strips. The incubation with $10^{-5}M$ hexamethonium (nicotinic receptor antagonist) significantly inhibited the magnitude of the nicotine associated contractions. The nicotine-induced contractions were not only significantly inhibited by pretreatment with $10^{-5}M$ indomethacin (nonspecific cyclooxygenase inhibitor) and with $10^{-6}M$ NS-398 (selective cyclooxygenase inhibitor), but also with $10^{-6}M$ Y-27632 (Rho kinase inhibitor). Ozagrel (thromboxane $A_2$ synthase inhibitor) and SQ-29548 (highly selective TP receptor antagonist) pretreatments significantly reduced the nicotine-induced contractile amplitude of the strips. High concentrations of nicotine caused contraction of isolated rabbit corpus cavernosal strips. This contraction appeared to be mediated by activation of nicotinic receptors. Rho-kinase and cyclooxygenase pathways, especially cyclooxygenase-2 and thromboxane $A_2$, might play a pivotal role in the mechanism associated with nicotine-induced contraction of the rabbit corpus cavernosum.

• Proceedings of the Korean Biophysical Society Conference
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• 2003.06a
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• pp.51-51
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• 2003

The medicinal plant Cimicifuga Racemosa (Black cohosh) has been used to treat many kinds of neuronal and menopausal symptoms, such as arthritis, menopausal depression, nerve pain, etc. Here, we examined the effect of Cimicifugoside (CF), one of triterpene glycosides which have been known as pharmacologically active ingredients of C. Racemosa, on nicotinic acetylcholine receptor (nAChR)-mediated catecholamine (CA) secretion in bovine adrenal chromaffin cell. Cimicifugoside inhibited calcium increase induced by 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP), a nAChR agonist with a half maximal inhibitory concentration (IC50) of 18${\pm}$2${\mu}$M. In contrast, cimicifugoside did not affect the calcium increases evoked by high K$\^$+/, veratridine, and bradykinin. The DMPP-induced sodium increase was also inhibited by cimicifugoside with IC50 of 2${\pm}$0.3${\mu}$M, suggesting that the activity of nAChRs is inhibited by cimicifugoside. Cimicifugoside did not effect on the KCl-induced secretion but markedly inhibited the DMPP-induced catecholamine secretion which was monitored by carbon-fiber amperometry in real time, and by high performance liquid chromatography (HPLC) through electrochemical detection. The results suggest that cimicifugoside selectively inhibits nAChR-mediated response in bovine chromaffin cells.

• BMB Reports
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• v.45 no.5
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• pp.275-280
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• 2012

Nicotinic acetylcholine receptors (nAChRs) are a diverse family of homo- or heteropentameric ligand-gated ion channels. Understanding the physiological role of each nAChR subtype and the key residues responsible for normal and pathological states is important. ${\alpha}$-Conotoxin neuropeptides are highly selective probes capable of discriminating different subtypes of nAChRs. In this study, we performed homology modeling to generate the neuronal ${\alpha}3$, ${\beta}2$ and ${\beta}4$ subunits using the x-ray structure of the ${\alpha}1$ subunit as a template. The structures of the extracellular domains containing ligand binding sites in the ${\alpha}3{\beta}2$ and ${\alpha}3{\beta}4$ nAChR subtypes were constructed using MD simulations and ligand docking processes in their free and ligand-bound states using ${\alpha}$-conotoxin GIC, which exhibited the highest ${\alpha}3{\beta}2$ vs. ${\alpha}3{\beta}4$ discrimination ratio. The results provide a reasonable structural basis for such a discriminatory ability, supporting the idea that the present strategy can be used for future investigations on nAChR-ligand complexes.