Kanemasa T, Asakura K, Ninomiya M
Discovery Research Laboratories II, Shionogi & Co. Ltd., Toyonaka, Osaka, Japan.
Brain Res. 1995 Dec 8;702(1-2):207-12. doi: 10.1016/0006-8993(95)01049-3.
The effects of U50488, kappa-opioid agonist on P-type Ca2+ channels, were studied. U50488 inhibited depolarization-induced Ca2+ uptake into rat brain synaptosomes, which was sensitive to omega-Agatoxin IVA (omega-AgaIVA; P-type Ca2+ channel blocker) and inhibited P-type Ca2+ channel currents recorded from rat cerebellar Purkinje neurons by the whole-cell patch clamp method. Dynorphin A also inhibited P-type Ca2+ channel currents. The inhibition by U50488 was biphasic; high affinity component (21%, IC50 = 8.9 x 10(-8) M) and low affinity component (79%, IC50 = 1.1 x 10(-5) M). At low concentrations of U50488 (10(-6) M), P-type Ca2+ channel current inhibition was attenuated by norbinartorphimine (nor-BNI), kappa-opioid antagonist, and by dialysis of cells with a pipette solution containing guanosine 5'-O-(2-thiodiphosphate) (GDP-beta S). At high concentrations of U50488 (10(-5) M), P-type Ca2+ channel current inhibition was frequency-dependent. Thus U50488-induced current inhibition is mediated by two mechanisms. Its high affinity component is produced by activation of kappa-opioid receptors, whereas the low affinity component is due to its direct action on the P-type Ca2+ channel.
研究了κ-阿片受体激动剂U50488对P型Ca2+通道的作用。U50488抑制去极化诱导的Ca2+摄取到大鼠脑突触体中，该摄取对ω-芋螺毒素IVA（ω-AgaIVA；P型Ca2+通道阻滞剂）敏感，并通过全细胞膜片钳法抑制从大鼠小脑浦肯野神经元记录的P型Ca2+通道电流。强啡肽A也抑制P型Ca2+通道电流。U50488的抑制作用呈双相性；高亲和力成分（21%，IC50 = 8.9×10(-8) M）和低亲和力成分（79%，IC50 = 1.1×10(-5) M）。在低浓度的U50488（10(-6) M）时，κ-阿片受体拮抗剂去甲纳曲酮（nor-BNI）以及用含有鸟苷5'-O-(2-硫代二磷酸)（GDP-βS）的移液管溶液对细胞进行透析可减弱P型Ca2+通道电流的抑制。在高浓度的U50488（10(-5) M）时，P型Ca2+通道电流抑制呈频率依赖性。因此，U50488诱导的电流抑制由两种机制介导。其高亲和力成分是由κ-阿片受体激活产生的，而低亲和力成分是由于其对P型Ca2+通道的直接作用。
