钙在可卡因所致猫脾条超敏反应中作用的研究。

Investigation of the role of calcium in the supersensitivity produced by cocaine in cat spleen strips.

作者信息

Summers R J, Tillman J

出版信息

Br J Pharmacol. 1979 Apr;65(4):689-99. doi: 10.1111/j.1476-5381.1979.tb07883.x.

DOI:10.1111/j.1476-5381.1979.tb07883.x

PMID:435692

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1668676/

Abstract

Cocaine (2 x 10(-6) M and 10(-5) M) produced 2 and 7 fold shifts to the left of the dose-response curve to (-)-noradrenaline recorded isotonically in isolated splenic capsular strips of the cat. 2. The same concentrations of cocaine also produced increases in the maximum response of the tissue to 117% and 126.7% of control. 3. Desmethylimipramine (DMI, 10(-7) to 10(-6) M) produced no significant potentiation of the response of cat spleen strips to (-)-noradrenaline. At 10(-5) M DMI decreased the maximum response. 4. Cocaine (10(-5) M) produced a 3.3 fold shift to the left of the dose-response curve whereas DMI (10(-6) M) had no effect on the dose-response curve to oxymetazoline in cat splenic capsular strips. 5. Cocaine (10(-5) M) in the presence of phentolamine (10(-6) M) produced a shift to the left and an increase in the maximum response to K+, an agonist which is believed to produce muscle contraction by increasing the membrane calcium flux. 6. Cocaine (10(-5 M) had no effect on the dose-response curve to angiotensin which is believed to contract vascular muscle by releasing calcium from intracellular storage sites. 7. The potentiating effect of cocaine (10(-5) M) on responses of spleen strips to (-)-noradrenaline was blocked by the calcium flux inhibitor SKF 525A (2.65 x 10(-5) M). 8. It is concluded that the results are compatible with the view that cocaine enhances the influx of calcium across the cell membrane during responses to agonists that utilize the extracellular pool of calcium and that this effect is responsible for a large part of the potentiation of the response.

摘要

可卡因（2×10⁻⁶M和10⁻⁵M）使猫离体脾包膜条带中以等张方式记录的对（-）-去甲肾上腺素的剂量-反应曲线向左移动了2倍和7倍。2. 相同浓度的可卡因还使组织对去甲肾上腺素的最大反应增加到对照的117%和126.7%。3. 去甲丙咪嗪（DMI，10⁻⁷至10⁻⁶M）对猫脾条带对（-）-去甲肾上腺素的反应无明显增强作用。在10⁻⁵M时，DMI降低了最大反应。4. 可卡因（10⁻⁵M）使剂量-反应曲线向左移动3.3倍，而DMI（10⁻⁶M）对猫脾包膜条带中对羟甲唑啉的剂量-反应曲线无影响。5. 在酚妥拉明（10⁻⁶M）存在的情况下，可卡因（10⁻⁵M）使对K⁺的反应曲线向左移动并使最大反应增加，K⁺是一种被认为通过增加膜钙通量来产生肌肉收缩的激动剂。6. 可卡因（10⁻⁵M）对血管紧张素的剂量-反应曲线无影响，血管紧张素被认为通过从细胞内储存部位释放钙来收缩血管平滑肌。7. 可卡因（10⁻⁵M）对脾条带对（-）-去甲肾上腺素反应的增强作用被钙通量抑制剂SKF 525A（2.65×10⁻⁵M）阻断。8. 得出的结论是，这些结果与以下观点一致：可卡因在对利用细胞外钙池的激动剂的反应过程中增强了钙跨细胞膜的内流，并且这种作用是反应增强的很大一部分原因。