• BMB Reports
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• 제34권6호
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• pp.573-577
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• 2001

The mammalian heart is known to undergo significant mechanical changes during fetal and neonatal development. The objective of this study was to define the ontogeny of the ryanodine receptor/$Ca^{2+}$ release channel and SERCA that play the major roles in excitation-contraction coupling. Whole ventricular homogenates of fetal (F) (19 and 22 days in gestation), postnatal (N) (1 and 7 days postnatal), and adult (A) (5 weeks postnatal) Sprague-Dawley rat hearts were used to study [$^3H$]ryanodine binding and oxalate-supported $^{45}Ca^{2+}$ uptake. For the ryanodine receptor, the major findings were: (1) The ryanodine receptor density, as determined by maximal [$^3H$]ryanodine binding ($B_{max}$), increased 3 fold between the F22 and A periods ($0.26{\pm}0.1$ vs. $0.73{\pm}0.07$ pmoles/mg protein, p<0.01), whereas there was no significant change during the F22 and N1 development phases ($0.26{\pm}0.1$ vs. $0.34{\pm}0.01$). (2) Affinity of the ryanodine receptor to ryanodine did not significantly change, as suggested by the lack of change in the $K_d$ during the development and maturation. For SERCA, changes started early with an increased rate of $Ca^{2+}$ uptake in the fetal periods (F19: $8.1{\pm}1.1$ vs. F22: $19.3{\pm}2.2$ nmoles/g protein/min; p<0.05) and peaked by 7 days (N7) of the postnatal age ($34.9{\pm}2.1$). Thus, we conclude that the quantitative changes occur in the ryanodine receptor during myocardial development. Also, the maturation of the $Ca^{2+}$ uptake appears to start earlier than that of the $Ca^{2+}$ release.

• KSBB Journal
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• 제32권2호
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• pp.108-116
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• 2017

Omeprazole, a benzimidazole derivative, suppresses gastric acid secretion by inhibiting $H^+/K^+$ ATPase in gastric parietals cells, and by reducing $H^+$ concentration. To improve stability of esomeprazole magnesium dihydrate (ESMD), enteric-coated preperation was composed of core tablet, subcoating and enteric coating layer. We were evaluated in vitro dissolution characteristics between test and reference ESMD preparation and stability. We could prepare enteric-coated formulation of ESMD by controlling disintegrating agent and coating ratio which could rapidly dissolved in neutral or alkali medium. The formulation D5 with crospovidone of 1.25% and coating ratio of 16.25% had a similar dissolution behavior compare to reference preparation. Difference factor ($f_1$) and similarity factor ($f_2$) were 0~15 and 50~100 and there was no significant difference in bioequivalence between formulations. The content and dissolution rate of formulation D5 were $96.54{\pm}0.21$ and $78.56{\pm}0.87%$ without change of color in accelerated condition ($40^{\circ}C$, RH 75%, high density polyethylene (HDPE) container) for 6 months. This study concluded that our enteric coated preparation of ESMD could be an useful method to improve stability of unstable drug without direct contact with coating material.

• Archives of Pharmacal Research
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• 제29권5호
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• pp.375-383
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• 2006

The anti platelet effects of a novel guanidine derivative, KR-32570 ([5-(2-methoxy-5-chlorophenyl) furan-2-ylcarbonyl]guanidine), were investigated with an emphasis on the mechanisms underlying its inhibition of collagen-induced platelet aggregation. KR-32570 significantly inhibited the aggregation of washed rabbit platelets induced by collagen $(10{\mu}g/mL)$, thrombin (0.05 U/mL), arachidonic acid $(100{\mu}M)$, a thromboxane (TX) $A_2$ mimetic agent U46619 (9,11-dideoxy-9,11-methanoepoxy-prostaglandin $F_2,\;1{\mu}M$) and a $Ca^{2+}$ ATPase inhibitor thapsigargin $(0.5{\mu}M)$ ($IC_{50}$ values: $13.8{\pm}1.8,\;26.3{\pm}1.2,\;8.5{\pm}0.9,\;4.3{\pm}1.7\;and\;49.8{\pm}1.4{\mu}M$, respectively). KR-32570 inhibited the collagen-induced liberation of $[^3H]$arachidonic acid from the platelets in a concentration dependent manner with complete inhibition being observed at $50{\mu}M$. The $TXA_2$ synthase assay showed that KR-32570 also inhibited the conversion of the substrate $PGH_2$ to $TXB_2$ at all concentrations. Furthermore, KR-32570 significantly inhibited the $[Ca^{2+}]_i$ mobilization induced by collagen at $50{\mu}M$, which is the concentration that completely inhibits platelet aggregation. KR-32570 also decreased the level of collagen $(10{\mu}g/mL)$induced secretion of serotonin from the dense-granule contents of platelets, and inhibited the NHE-1-mediated rabbit platelet swelling induced by intracellular acidification. These results suggest that the antiplatelet activity of KR-32570 against collagen-induced platelet aggregation is mediated mainly by inhibiting the release of arachidonic acid, $TXA_2$ synthase, the mobilization of cytosolic $Ca^{2+}$ and NHE-1.

• 대한약리학회지
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• 제20권1호
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• pp.55-65
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• 1984

[$PGF_{2{\alpha}}$]의 rat적출심방에 대한 작용을 ouabain의 작용과 비교하여 다음과 같은 결과를 얻었다. $PGF_{2{\alpha}}$의 양성변력성작용은 ouabain의 작용에 비해 potency가 강하고 efficacy는 낮았다. Ouabain은 $PGF_{2{\alpha}}$의 양성변시성작용과 유사한 양성변시성 경향을 나타내었는데 이 점에 대해 추후의 탐구가 요구된다. $PGF_{2{\alpha}}(3{\pm}10^{-8}M)$의 작용은 저칼슘농도(1.4mM)에서 ouabain$(3{\pm}10^{-3}M)$보다 현저히 $({\leq}0.05{\sim}p{\leq}0.00)$강하게 나타났고, medium내에 첨가되는 $Ca^{++}$에 대하여도 보다 예민하게 반응하였다. 저칼륨 medium(2.8mM) 또는 medium내 $K^+$첨가는 $PGF_{2{\alpha}}$보다 ouabain의 작용에 더 큰 영향을 미쳤다. $PGF_{2{\alpha}}$와 ouabain의 작용에 미치는 lidocaine ($1{\pm}10^{-5}M$이상의 고농도)의 영향은 매우 흡사하여 별다른 차이점을 볼 수 없었다. Propranolol $(3{\pm}10^{-6}M)$로써 전처치하여 아드레나린성 ${\beta}$수용체를 봉쇄한 적출심방에서 $PGF_{2{\alpha}}$ 양성변력성 및 양성변시성 작용은 방해를 받지 않았다. 이상의 결과로 보아 $PGF_{2{\alpha}}$는 ouabain의 $Na^+$, $K^+$-ATPase 억제기전파는 달리 $PGF_{2{\alpha}}$ 고유의 막수용체에 작용하여 $Ca^{++}$의 세포내 유입을 촉진시키는 기전으로 작용하는 것으로 추측되며, 그 수용체의 등정(identification)은 추후의 연구과제로 남는다.