• 약학회지
• /
• 제45권3호
• /
• pp.282-286
• /
• 2001

To investigate the different mechanism between ATP and compound 48/80 (C$_{48}$80/)-induced histamine release, we observed effects of calcium antagonists in histamine release of rat peritoneal mast cells. Verapamil and diltiazem (voltage-dependent calcium channel blocker) and TMB-8 (a blocker of intracellular calcium release) significantly inhibited ATP-induced histamine release, but did not inhibit $C_{48}$80/-induced histamine release. Econazole (a blocker of receptor-operated calcium channel) dose-dependently inhibited both ATP and $C_{48}$80/-induced histamine release, but inhibitory effect of econazole in ATP-induced histamine release was more potent than that in $C_{48}$80/-induced histamine. EGTA dose-dependently inhibited ATP and $C_{48}$80/-induced histamine release, but $C_{48}$80/-induced histamine release was slightly inhibited by high concentrations (>2 mM) of EGTA. These results suggest that ATP-induced histamine release is related to broth intracellular calcium release and extracellular calcium influx via voltage-dependent calcium channel and receptor-operated calcium channel. $C_{48}$80/-induced histamine release is related to extracellular calcium influx, especially by receptor-operated calcium channel rather than voltage-dependent calcium channel.

• Biomolecules & Therapeutics
• /
• 제15권3호
• /
• pp.156-161
• /
• 2007

Rapid advances in pharmacogenomic research have provided important information to improve drug selection, to maximize drug efficacy, and to minimize drug adverse reaction. The SNPs that are the most abundant type of genetic variants have been proven as valid biomarkers to give information on the prediction of pharmacokinetic/pharmacodynamic properties of drugs based on genotype. In order to elucidate a correlation between SNPs of calcium channel encoding gene and adverse reactions of calcium channel blockers, we investigated SNPs in CACNA1C gene known as a binding site of calcium channel blocker. 96 patients with hypertension who had taken or are taking an antihypertensive drug, 1,4-dihydropyridine (DHP) were included for analysis. These patients were composed of 47 patients with adverse drug reactions (ADR) such as edema from calcium channel blockers and 49 patients without ADR as a control group. The exons encoding the drug binding sites were amplified by PCR using specific primers, and SNPs were analyzed by direct sequencing. We found that there was no SNP in the exons encoding DHP binding site, but four novel SNPs in the exon-intron junction region. However, four novel SNPs were not associated with the ADR of calcium channel blockers. In conclusion, this study showed that ADR from calcium channel blockers may not be caused by SNPs of the binding sites of calcium channel blockers in CACNA1C gene.

• 대한화학회지
• /
• 제57권1호
• /
• pp.99-103
• /
• 2013

The present communication deals with the Pharmacophore modeling, 3D QSAR and docking analysis on series of Pyrimidine derivatives as potential calcium channel blockers. The computational studies showed hydrogen bond donor, hydrogen bond acceptor, and hydrophobic group are important features for calcium channel blocking activity. These studies showed that Pyrimidine scaffold can be utilized for designing of novel calcium channels blockers for CVS disorders.

• 대한약리학회지
• /
• 제31권3호
• /
• pp.355-363
• /
• 1995

Calcium수송에 대한 기전을 추구하기위하여, carbachol을 사용하여 ml muscarinic receptor-transfected RBL-2H3 cell-line에서 다음과 같은 실험결과를 얻었기에 이에 보고한다. 1) Carbachol의 투여로 이들 cell-line에서 $Ca^{2+}$ influx가 농도에 따라 증가하였고, hexosaminidase 분비양도 의의있게 증가하였다. 2) Atropine 투여로 Carbachol의 상승작용이 의의있게 억제되었다. 3) 수종의 금속양이온을 투여하여 carbachol의 $Ca^{2+}$수송에 대한 영향을 관찰한 바, 이들 금속이온들은 $Ca^{2+}$의 influx를 의의있게 억제하였다. 4) PMA(20 nM) 투여로 carbachol의 hexosaminidase의 분비는 억제되지 못했지만 $Ca^{2+}$ influx는 억제되었다. 5) PTx $(0.2\;{\mu}g/ml)$ 투여로 carbachol의 hexosaminidase 분비가 의의있게 억제되었다. 위의 결과로 미루어 보아, 이 세포의 muscarinic receptor가 calcium channel을 통한 calcium수송에 매우 중요한 영향을 나타내는데, 이들 calcium ion channel은 적어도 두 종류가 존재하며, 하나는G-protein-dependent calcium channel에 의하며, 다른 하나는 G-protein-independent calcium channel에 대한 작용에 의한 것으로 생각된다. 또한 이 calcium channel들은 2가 또는 3가의 다른 금속 ion들에 의하여 calcium수송이 억제된다.

• The Korean Journal of Physiology and Pharmacology
• /
• 제4권6호
• /
• pp.427-437
• /
• 2000

The early studies of cardiac and smooth muscle cells provided evidence for two different calcium channels, the L-type (also called high-voltage activated [HVA]) and T-type (low-voltage activated [LVA]). These calcium channels provided calcium for muscle contractions and pace-making activities. As might be expected, the number of different calcium channels increased when researchers studied neurons and the identification of the neuronal calcium channels has proven to be much more difficult than with the muscle calcium channels. There are two reasons for this difficulty; (1) a larger number of different calcium channels in neurons and (2) many of the different calcium channels have similar kinetic properties. This review uses the N-type calcium channel to illustrate the difficulties in identifying and characterizing calcium channels in neurons. It shows that the discovery of toxins that can specifically block single calcium channel types has made it possible to easily and rapidly discern the physiological roles of the different calcium channels in the neuron, Without these toxins it is unlikely that progress would have been as rapid.

• The Korean Journal of Physiology and Pharmacology
• /
• 제23권3호
• /
• pp.219-227
• /
• 2019

Polycystic kidney disease 2-like-1 (PKD2L1), polycystin-L or transient receptor potential polycystin 3 (TRPP3) is a TRP superfamily member. It is a calcium-permeable non-selective cation channel that regulates intracellular calcium concentration and thereby calcium signaling. Although the calmodulin (CaM) inhibitor, calmidazolium, is an activator of the PKD2L1 channel, the activating mechanism remains unclear. The purpose of this study is to clarify whether CaM takes part in the regulation of the PKD2L1 channel, and if so, how. With patch clamp techniques, we observed the current amplitudes of PKD2L1 significantly reduced when co-expressed with CaM and $CaM{\triangle}N$. This result suggests that the N-lobe of CaM carries a more crucial role in regulating PKD2L1 and guides us into our next question on the different functions of two lobes of CaM. We also identified the predicted CaM binding site, and generated deletion and truncation mutants. The mutants showed significant reduction in currents losing PKD2L1 current-voltage curve, suggesting that the C-terminal region from 590 to 600 is crucial for maintaining the functionality of the PKD2L1 channel. With PKD2L1608Stop mutant showing increased current amplitudes, we further examined the functional importance of EF-hand domain. Along with co-expression of CaM, ${\triangle}EF$-hand mutant also showed significant changes in current amplitudes and potentiation time. Our findings suggest that there is a constitutive inhibition of EF-hand and binding of CaM C-lobe on the channel in low calcium concentration. At higher calcium concentration, calcium ions occupy the N-lobe as well as the EF-hand domain, allowing the two to compete to bind to the channel.

• Molecules and Cells
• /
• 제21권3호
• /
• pp.315-329
• /
• 2006

Two, well characterized cationic channels, the ryanodine receptor (RyR) and the canonical transient receptor potential cation channel (TRPC) are briefly reviewed with a particular attention on recent developments related to the interplay between the two channel families.

• 대한약리학회지
• /
• 제22권2호
• /
• pp.151-156
• /
• 1986

최근 심근세포 또는 신경세포에서 발표된 여러 종류의 calcium channel중 calcium antagonist로 차단되는 channel 또는 차단되지 않는 channel 등이 있는지 알아보기 위해 실험을 시행하였다. 돼지 소장 평활근으로부터 고농도의 KCl(150mM)로 부하된 세포 포막낭을 만들어 고농도의$K^+$ 또는 전기자극으로 $^{45}Ca$의 이동을 유발시켜 다음과 같은 성적을 얻었다. 저농도의 $K^+$용액에서의 $^{45}Ca$이동보다 고농도의 $K^+$-용액에서의 $^{45}Ca$이동이 유의하게 증가되었으며(p<0. 05) 이때 유입되는 $^{45}Ca$의 양은 시간에 따라 서서히 감소되었다. 전기자극(3V, 15Hz, 25msec)을 하였을때 유입되는 $^{45}Ca$의 양은 전기자극을 하지 않은 대조군에 비하여 현저하게 증가되었고, 자극시간에 따른 $^{45}Ca$의 유입량은 2분 동안 계속 증가되었다. Diltiazem 또는 nifedipine을 처치하였을때, 고농도의 $K^+$-용액에 의한 $^{45}Ca$의 유입은 억제되지 않았으나 전기자극에 의해 유도되는 $^{45}Ca$의 유입은 유의하게 억제되었다(p<0.005). 상기의 실험성적으로 돼지 소장 평활근으로부터 분리한 세포막에서의 calcium이동 중 전기자극에 의해 이루어지는 것은 calcium antagonist로 차단되는 calcium channel을 통하여 이루어지는 것으로 사료된다.

• The Korean Journal of Physiology and Pharmacology
• /
• 제10권5호
• /
• pp.255-261
• /
• 2006

Melittin-induced nociceptive responses are mediated by selective activation of capsaicin-sensitive primary afferent fibers and are modulated by excitatory amino acid receptor, cyclooxygenase, protein kinase C and serotonin receptor. The present study was undertaken to investigate the peripheral and spinal actions of voltage-gated calcium channel antagonists on melittin-induced nociceptive responses. Changes in mechanical threshold and number of flinchings were measured after intraplantar (i.pl.) injection of melittin $(30\;{\mu}g/paw)$ into mid-plantar area of hindpaw. L-type calcium channel antagonists, verapamil [intrathecal (i.t.), 6 or $12\;{\mu}g$; i.pl.,100 & $200\;{\mu}g$; i.p., 10 or 30 mg], N-type calcium channel blocker, ${\omega}-conotoxin$ GVIA (i.t., 0.1 or $0.5\;{\mu}g$; i.pl., $5\;{\mu}g$) and P-type calcium channel antagonist, ${\omega}-agatoxin$ IVA (i.t., $0.5\;{\mu}g$; i.pl., $5\;{\mu}g$) were administered 20 min before or 60 min after i.pl. injection of melittin. Intraplantar pre-treatment and i.t. pre- or post-treatment of verapamil and ${\omega}-conotoxin$ GVIA dose-dependently attenuated the reduction of mechanical threshold, and melittin-induced flinchings were inhibited by i.pl. or i.t. pre-treatment of both antagonists. P-type calcium channel blocker, ${\omega}-agatoxin$ IVA, had significant inhibitory action on flinching behaviors, but had a limited effect on melittin-induced decrease in mechanical threshold. These experimental findings suggest that verapamil and ${\omega}-conotoxin$ GVIA can inhibit the development and maintenance of melittin-induced nociceptive responses.

• The Korean Journal of Physiology and Pharmacology
• /
• 제2권1호
• /
• pp.55-62
• /
• 1998

${\alpha},\;{\beta}-Adrenergics$, and calcium channels were known to be related to inducing cardiac hypertrophy. Recently, it was reported that the cardiac renin-angiotensin system (RAS) was an important factor in ventricular hypertrophy. The present study was aimed to investigate the effects of ${\alpha},\;{\beta}-adrenergic$, and calcium channel blockers that might be involved in the regulation of cardiac RAS. The reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the expression of renin gene in the perfused rat heart. Changes in angiotensin converting enzyme (ACE) activity and cyclic AMP (cAMP) content which were thought to play a role in inducing cardiac hypertrophy were measured in the perfused rat heart. The expression of renin gene was not only increased by isoproterenol with metoprolol-pretreatment but also increased by vasopressin treatment in the presence of calcium channel blocker, nifedipine or verapamil. Either prazosin alone or norepinephrine with prazosin-pretreatment significantly increased the ACE activity. However, isoproterenol with metoprolol-pretreatment significantly decreased the ACE activity. On the other hand, the ACE activity was not changed by vasopressin, nifedipine, or verapamil treatments. The content of cAMP was significantly increased by either isoproterenol or vasopressin treatment. According to these results, renin gene expression was associated with ${\beta}2$ - adrenoceptor and calcium channel. ACE activity was associated with ${\alpha}-\;and{\beta}2$ - adrenoceptor. In conclusion, ${\beta}2$ - adrenoceptor was important in cardiac renin gene expression and ACE activity and ${\alpha},\;{\beta}$ -adrenergic, and calcium channel blockers might be involved in the regulation of cardiac RAS in a complicated way.