Messineo F C, Katz A M
J Cardiovasc Pharmacol. 1979 Jul-Aug;1(4):449-59. doi: 10.1097/00005344-197907000-00007.
The effects of the beta-adrenergic receptor blocking agents propranolol and timolol on the initial calcium uptake velocity of sarcoplasmic reticulum vesicles of rabbit skeletal muscle were studied. Racemic d- and l-propranolol had similar inhibitory effects on initial calcium uptake velocity, which was inhibited 50% by 5--7 X 10(-4) M racemic propranolol. Timolol was a much less potent inhibitor of initial calcim uptake velocity; 50% inhibition occurred at approximately 10(-2) M timolol. Both drugs inhibited maximal calcium uptake velocity; however, KCa (the Ca2+ concentration at which calcium uptake was half-maximal) was modified differently. Propranolol increased KCa, whereas timolol caused the KCa to decrease. Addition of either drug to an ongoing calcium uptake reaction at the time that calcium content became maximal caused renewed calcium uptake. The relative potencies of propranolol and timolol as negative inotropic agents are similar to their potencies as inhibitors of sarcoplasmic reticulum calcium uptake, but dissimilar to their beta-adrenergic receptor blocking potencies. Timolol, which has been reported to have less negative inotropic effect than propranolol, is approximately 5 time more potent than propranolol as a beta-adrenergic receptor blocking agent but 15 times less potent as an inhibitor of sarcoplasmic reticulum calcium uptake. Inhibition of sarcoplasmic reticulum calcium uptake may thus characterize negative inotropic potencies of new beta-adrenergic receptor blocking agents.
研究了β-肾上腺素能受体阻滞剂普萘洛尔和噻吗洛尔对兔骨骼肌肌浆网囊泡初始钙摄取速度的影响。消旋的d-和l-普萘洛尔对初始钙摄取速度具有相似的抑制作用，5-7×10⁻⁴M消旋普萘洛尔可抑制50%。噻吗洛尔对初始钙摄取速度的抑制作用要弱得多；约10⁻²M噻吗洛尔时出现50%的抑制。两种药物均抑制最大钙摄取速度；然而，KCa（钙摄取达到最大摄取量一半时的Ca²⁺浓度）的变化不同。普萘洛尔使KCa升高，而噻吗洛尔使KCa降低。在钙含量达到最大时，向正在进行的钙摄取反应中加入任何一种药物都会导致再次出现钙摄取。普萘洛尔和噻吗洛尔作为负性肌力药物的相对效力与其作为肌浆网钙摄取抑制剂的效力相似，但与其β-肾上腺素能受体阻断效力不同。据报道，噻吗洛尔的负性肌力作用比普萘洛尔小，作为β-肾上腺素能受体阻断剂，其效力约为普萘洛尔的5倍，但作为肌浆网钙摄取抑制剂的效力则比普萘洛尔低15倍。因此，肌浆网钙摄取的抑制可能是新的β-肾上腺素能受体阻断剂负性肌力作用的特征。
