Reggiani A, Carenzi A, Della Bella D
Zambon Farmaceutici S.p.A., Research Laboratories, Bresso-Milan, Italy.
Brain Res. 1987 Oct 13;423(1-2):254-60. doi: 10.1016/0006-8993(87)90847-x.
Opioids' modulation of beta-receptors' density and function has been investigated in a cultured cell line system. Rat C6 glioma cells do not have opioid receptors or, at least, the number of these receptors is very low, but cell exposure to desmethylimipramine (DMI) causes expression of functional opioid receptors as indicated by the increased [3H]DHM binding and by the acquired ability of opioids to inhibit ISO-stimulated cAMP accumulation. Cell exposure to DMI also causes beta-receptors' down-regulation as indicated by the decline in [3H]DHA binding coupled to a reduced ability of isoproterenol (ISO) to stimulate cAMP accumulation in intact cells. In the present paper we show that cell exposure to opioid agonists during DMI treatment counteracted DMI-induced beta-receptor loss. Similarly, opioid agonists added at the beginning of ISO exposure in DMI-pretreated cells, inhibited ISO-induced beta-receptor tachyphylaxis. These results suggest that opioids may exert a protective effect on beta-receptor function and this appears to be a common mechanism which is operant when overstimulation of beta-receptors takes place.
在一个培养细胞系系统中，已对阿片类药物对β受体密度和功能的调节作用进行了研究。大鼠C6胶质瘤细胞没有阿片受体，或者至少这些受体的数量非常少，但细胞暴露于去甲丙咪嗪（DMI）会导致功能性阿片受体的表达，这表现为[3H]DHM结合增加以及阿片类药物抑制ISO刺激的cAMP积累的能力增强。细胞暴露于DMI还会导致β受体下调，这表现为[3H]DHA结合减少，同时异丙肾上腺素（ISO）刺激完整细胞中cAMP积累的能力降低。在本论文中，我们表明在DMI处理期间细胞暴露于阿片类激动剂可抵消DMI诱导的β受体丧失。同样，在DMI预处理细胞中ISO暴露开始时添加阿片类激动剂，可抑制ISO诱导的β受体快速耐受。这些结果表明，阿片类药物可能对β受体功能发挥保护作用，这似乎是在β受体过度刺激时起作用的一种常见机制。
