Ahlner J, Axelsson K L, Karczewski P, Andersson R G
Department of Clinical Pharmacology, University Hospital, Linköping, Sweden.
Pharmacol Toxicol. 1990 Apr;66(4):277-82. doi: 10.1111/j.1600-0773.1990.tb00747.x.
It was recently observed that the relaxation induced by glyceryl trinitrate (GTN) showed a biphasic concentration-response curve; a high-sensitivity component represented by concentrations less than 1 nM and a low-sensitivity component represented by concentrations greater than 1 nM. The effect of two glyceryl trinitrate concentrations (0.1 nM and 1 microM) were tested on the uptake of 45Ca2+ to tissue pieces of bovine mesenteric arteries (BMA) as well as on the uptake of 45Ca2+ to a microsomal preparation of BMA. The effect of GTN and 8-Br-cGMP was also studied on the IP3-induced release of Ca2+ from the microsomal preparation preloaded with 45Ca2+. The influence of IP3 and GTN on the activity of Ca2(+)-ATPase in the microsomal preparation was tested as well. The phenylephrine-stimulated uptake of Ca2+ to tissue pieces of BMA was significantly reduced by the high GTN-concentration (1 microM) but not by the lower concentration. The uptake of Ca2+ to the microsomal preparation was significantly stimulated by the two GTN-concentrations tested, as well as by 8-Br-cGMP (0.1 mM). The calcium release induced by IP3 (1 microM) from the microsomal preparation was inhibited by both the low and the high GTN-concentration and by 8-Br-cGMP (0.1 mM). The Ca2(+)-ATPase activity was stimulated by both GTN-concentrations tested while it was inhibited by IP3. It is concluded that GTN is able to induce a reduction of the free intracellular Ca2+ by several mechanisms, which are of importance for the relaxation represented by the high-affinity component. The low-affinity component in addition reduces the inflow of Ca2+ over the plasma membrane.
最近观察到，硝酸甘油（GTN）诱导的舒张呈现双相浓度-反应曲线；低浓度（小于1 nM）代表高敏感性成分，高浓度（大于1 nM）代表低敏感性成分。测试了两种硝酸甘油浓度（0.1 nM和1 μM）对牛肠系膜动脉（BMA）组织块摄取45Ca2+以及对BMA微粒体制剂摄取45Ca2+的影响。还研究了GTN和8-溴-cGMP对预先加载45Ca2+的微粒体制剂中IP3诱导的Ca2+释放的影响。同时测试了IP3和GTN对微粒体制剂中Ca2(+)-ATP酶活性的影响。高浓度GTN（1 μM）可显著降低去氧肾上腺素刺激的BMA组织块对Ca2+的摄取，而低浓度则无此作用。测试的两种GTN浓度以及8-溴-cGMP（0.1 mM）均显著刺激了微粒体制剂对Ca2+的摄取。IP3（1 μM）诱导的微粒体制剂中Ca2+释放受到低浓度和高浓度GTN以及8-溴-cGMP（0.1 mM）的抑制。测试的两种GTN浓度均刺激了Ca2(+)-ATP酶活性，而IP3则抑制该活性。结论是，GTN能够通过多种机制诱导细胞内游离Ca2+减少，这些机制对于高亲和力成分所代表的舒张作用至关重要。此外，低亲和力成分还减少了Ca2+通过质膜的内流。
