Bunn S J, Dunkley P R
Neuroscience Group, Faculty of Medicine, University of Newcastle, NSW, Australia.
Biochem Pharmacol. 1991 Mar 1;41(5):715-22. doi: 10.1016/0006-2952(91)90071-c.
The ability of a number of opioid agonists and antagonists to affect nicotine-induced 45Ca2(+)-uptake into cultured bovine adrenal medullary cells has been investigated. High (10 microM) concentrations of the opioid agonist bremazocine produced a significant inhibition of nicotine-induced 45Ca2(+)-uptake throughout the 15 min time course examined. The opioid subtype-selectivity of this inhibition was investigated; mu and delta selective agonists produced only minor effects whereas the kappa selective agonist U50-488H and the endogenous opioid peptides dynorphin(1-13) and metorphamide almost abolished nicotine-induced 45Ca2(+)-uptake. The U50-488H inhibition was significant at 10 nM concentrations with an IC50 of approximately 1 microM. U50-488H inhibition could not be reversed or reduced by the opioid antagonists naxolone, diprenophine or Mr2266. Furthermore, Mr2266 and its optical isomer Mr2267 also produced marked inhibition of 45Ca2(+)-uptake. The inhibition was specific to nicotine-induced 45Ca2(+)-uptake in that a similar level of uptake evoked by potassium depolarization was unaffected by high concentrations of U50-488H. These data indicate that opioid inhibition of nicotine-induced 45Ca2(+)-uptake does not involve classical, stereospecific opioid receptors and suggests the involvement of a pharmacologically distinct opioid recognition site. It is speculated that this may be associated with the nicotine receptor-ionophore complex.
研究了多种阿片类激动剂和拮抗剂对尼古丁诱导的45Ca2(+)摄取进入培养的牛肾上腺髓质细胞的影响。在整个15分钟的检测时间过程中，高浓度（10 microM）的阿片类激动剂布瑞马唑嗪对尼古丁诱导的45Ca2(+)摄取产生了显著抑制作用。研究了这种抑制作用的阿片类亚型选择性；μ和δ选择性激动剂仅产生轻微影响，而κ选择性激动剂U50-488H以及内源性阿片肽强啡肽(1-13)和甲硫酰胺几乎完全消除了尼古丁诱导的45Ca2(+)摄取。U50-488H在10 nM浓度时的抑制作用显著，IC50约为1 microM。阿片类拮抗剂纳洛酮、二丙诺啡或Mr2266不能逆转或降低U50-488H的抑制作用。此外，Mr2266及其光学异构体Mr2267也对45Ca2(+)摄取产生了显著抑制作用。这种抑制作用对尼古丁诱导的45Ca2(+)摄取具有特异性，因为高浓度的U50-488H对钾去极化引起的类似摄取水平没有影响。这些数据表明，阿片类对尼古丁诱导的45Ca2(+)摄取的抑制作用不涉及经典的、立体特异性的阿片受体，并提示存在一个药理学上不同的阿片识别位点。据推测，这可能与尼古丁受体-离子载体复合物有关。
