Brent P J, Saunders H, Dunkley P R
Neuroscience Group, Faculty of Medicine and Health Sciences, University of Newcastle, NSW, Australia.
Neurosci Lett. 1996 Jun 21;211(2):138-42. doi: 10.1016/0304-3940(96)12711-7.
The sigma receptor ligands (+) and (-)pentazocine and BD1008 (1-100 microM) were added to rat forebrain synaptosomes. Their effects on intrasynaptosomal free calcium ([Ca2+(+)]i) levels under basal conditions and after depolarisation with high potassium buffer (45 mM KCl), veratridine (25 microM) and 4-aminopyridine (4-AP, 1 mM) were determined. The sigma ligands elicited significant, concentration-dependent decreases in basal [Ca2+]i levels with an order of potency (-)pentazocine > (+)pentazocine = BD1008. The sigma ligands (at the maximum effective concentrations) also significantly inhibited the rise in [Ca2+]i levels produced by depolarisation with KCl, veratridine and 4-AP. The effect of (+) and (-)pentazocine (100 microM) to inhibit the depolarisation-dependent increase in [Ca2+]i levels was greater when veratridine and 4-aminopyridine were used to depolarise the synaptosomes than with KCl, whereas the effect of BD1008 (100 microM) was approximately equipotent using all three depolarising agents. However, BD1008 was more potent to inhibit the KCl-induced rise in [Ca2+]i compared to (+) and (-)pentazocine. The data demonstrate for the first time that sigma ligands decrease [Ca2+]i levels in rat forebrain synaptosomes and this suggests a possible mechanism for the changes to neuronal protein phosphorylation and neurotransmitter release previously observed with sigma ligands.
将西格玛受体配体（+）和（-）喷他佐辛以及BD1008（1 - 100微摩尔）添加到大鼠前脑突触体中。测定了它们在基础条件下以及在用高钾缓冲液（45 mM KCl）、藜芦碱（25微摩尔）和4 - 氨基吡啶（4 - AP，1 mM）去极化后对突触体内游离钙（[Ca2 +（+）]i）水平的影响。西格玛配体在基础[Ca2 +]i水平上引起了显著的、浓度依赖性的降低，效力顺序为（-）喷他佐辛>（+）喷他佐辛 = BD1008。西格玛配体（在最大有效浓度下）也显著抑制了由KCl、藜芦碱和4 - AP去极化所产生的[Ca2 +]i水平的升高。当使用藜芦碱和4 - 氨基吡啶使突触体去极化时，（+）和（-）喷他佐辛（100微摩尔）抑制[Ca2 +]i水平依赖于去极化的升高的作用比用KCl时更大，而使用所有三种去极化剂时，BD1008（100微摩尔）的作用大致相当。然而，与（+）和（-）喷他佐辛相比，BD1008抑制KCl诱导的[Ca2 +]i升高的效力更强。这些数据首次证明西格玛配体降低大鼠前脑突触体中的[Ca2 +]i水平，这表明了一种可能的机制，可解释先前观察到的西格玛配体对神经元蛋白磷酸化和神经递质释放的影响。
