Caparrotta L, Fassina G, Froldi G, Poja R
Br J Pharmacol. 1987 Jan;90(1):23-30. doi: 10.1111/j.1476-5381.1987.tb16821.x.
Antagonism between (-)-N6-phenylisopropyladenosine (PIA) and the dihydropyridine calcium channel facilitator Bay K 8644 was investigated in guinea-pig spontaneously beating or electrically driven isolated atria, taken from normal and from reserpine-treated animals. PIA (3-100 nM) produced a dose-dependent decrease in contractile tension and frequency in spontaneously beating atria being more effective in reserpinized preparations. Bay K 8644 (5-200 nM) produced an increase in contractile tension in both normal and reserpinized atria. In electrically driven left atria the positive inotropic effect of Bay K 8644 was similar to that in spontaneously beating preparations. The positive chronotropic effect of Bay K 8644 was slight and variable. PIA produced a rightward parallel shift of the concentration-response curves for the positive inotropic effects of Bay K 8644 in all experimental conditions. In spontaneously beating atria from normal guinea-pigs, the Schild regression plot was linear and its slope near to unity; pA2 of PIA 8.63 +/- 0.05 (IC50 2.35 +/- 0.25 nM). In electrically driven atria the antagonism by PIA of the effects of Bay K 8644 was apparently competitive, and the IC50 of PIA was 18.6 +/- 0.4 nM. PIA antagonized the positive chronotropic effect of Bay K 8644 in spontaneously beating preparations, both from normal and from reserpine-treated animals. Carbachol did not modify the positive inotropic effects of Bay K 8644. These data indicate that PIA may interact with Bay K 8644 at the level of the slow calcium channels, and may decrease the transmembrane calcium flux into the cell.
在取自正常豚鼠和利血平处理过的豚鼠的自发性搏动或电驱动的离体心房中，研究了（-）-N6-苯异丙基腺苷（PIA）与二氢吡啶类钙通道促进剂Bay K 8644之间的拮抗作用。PIA（3-100 nM）可使自发性搏动心房的收缩张力和频率呈剂量依赖性降低，在利血平化制剂中更有效。Bay K 8644（5-200 nM）可使正常和利血平化心房的收缩张力增加。在电驱动的左心房中，Bay K 8644的正性肌力作用与自发性搏动制剂中的相似。Bay K 8644的正性变时作用轻微且多变。在所有实验条件下，PIA使Bay K 8644正性肌力作用的浓度-反应曲线向右平行移动。在正常豚鼠的自发性搏动心房中，Schild回归图呈线性，斜率接近1；PIA的pA2为8.63±0.05（IC50为2.35±0.25 nM）。在电驱动心房中，PIA对Bay K 8644作用的拮抗作用明显为竞争性，PIA的IC50为18.6±0.4 nM。PIA拮抗Bay K 8644在正常和利血平处理动物的自发性搏动制剂中的正性变时作用。卡巴胆碱不改变Bay K 8644的正性肌力作用。这些数据表明，PIA可能在慢钙通道水平与Bay K 8644相互作用，并可能减少跨膜钙流入细胞。
