Agata N, Tanaka H, Shigenobu K
Department of Pharmacology, Toho University School of Pharmaceutical Sciences, Chiba, Japan.
Br J Pharmacol. 1993 Mar;108(3):571-2. doi: 10.1111/j.1476-5381.1993.tb12842.x.
Cyclopiazonic acid (CPA), a mycotoxin from Aspergillus and Penicillium, has been described as a highly selective inhibitor of Ca(2+)-ATPase in the sarcoplasmic reticulum (SR) in skeletal and smooth muscles but no reports at present deal with the effect of CPA in cardiac muscle. In the present study, we examined the inotropic effect of CPA on adult and neonatal rat myocardia, the contractions of which are known to be highly dependent on Ca(2+)-release from the sarcoplasmic reticulum and transsarcolemmal Ca(2+)-influx, respectively. CPA (30 microM) produced a negative inotropic effect in adult preparations, accompanied by marked prolongation of the contraction duration. In contrast, CPA had minimum effects on neonatal myocardium. Thus we have demonstrated that CPA exerts negative inotropic effects on adult myocardium probably through inhibition of SR function.
环匹阿尼酸(CPA)是一种由曲霉属和青霉属产生的霉菌毒素,已被描述为骨骼肌和平滑肌肌浆网(SR)中Ca(2+)-ATP酶的高度选择性抑制剂,但目前尚无关于CPA对心肌作用的报道。在本研究中,我们研究了CPA对成年和新生大鼠心肌的变力作用,已知成年和新生大鼠心肌的收缩分别高度依赖于肌浆网释放Ca(2+)和跨肌膜Ca(2+)内流。CPA(30微摩尔)对成年大鼠心肌制剂产生负性变力作用,同时伴有收缩持续时间的显著延长。相比之下,CPA对新生大鼠心肌的作用最小。因此,我们证明CPA可能通过抑制肌浆网功能对成年大鼠心肌产生负性变力作用。