Kest B, Jenab S, Brodsky M, Sadowski B, Belknap J K, Mogil J S, Inturrisi C E
The College of Staten Island/City University of New York, Staten Island, NY 10314, USA.
Brain Res. 1999 Jan 23;816(2):381-9. doi: 10.1016/s0006-8993(98)01141-x.
The present study examined mu and delta opioid analgesia, receptor binding, and receptor mRNA levels in lines of mice from two selective breeding projects of relevance to opioid analgesia. Large differences were observed in the analgesic potency of [d-Ala2, NMPhe4, Gly-ol]enkephalin (DAMGO), [d-Pen2,5]enkephalin (DPDPE), and [d-Ala2]deltorphin II (DELT), selective mu, delta1, and delta2 opioid receptor agonists, respectively, in mice selectively bred for high (HA) and low (LA) swim stress-induced analgesia (SIA). HAR and LAR mice, selectively bred for high and low levorphanol analgesia, respectively, display equally large differences in their analgesic sensitivity to DAMGO, modest differences in sensitivity to DPDPE, and no differences in sensitivity to DELT. These sizable genotypic differences in analgesic potency were accompanied by HA/LA and HAR/LAR differences in whole-brain homogenate [3H]DPDPE and/or [3H]DELT, but paradoxically not [3H]DAMGO, binding. Solution hybridization of mRNA extracts encoding mu (MOR-1) or delta (DOR-1) opioid receptors indicated some regional differences in gene expression between high and low lines. Surprisingly, differences in these in vitro markers were often in the direction of LAR>HAR. The present data indicate that selection for either SSIA or levorphanol analgesia produces differential effects on mu and delta opioid analgesia that are accompanied by alterations on in vitro assays, the significance of which remains to be determined. The data are discussed with regard to the utility of in vitro biological markers and genetic models of analgesia.
本研究检测了来自与阿片类镇痛相关的两个选择性育种项目的小鼠品系中的μ和δ阿片类镇痛、受体结合及受体mRNA水平。分别作为选择性μ、δ1和δ2阿片受体激动剂的[D - Ala2，N - Mphe4，Gly - ol]脑啡肽（DAMGO）、[D - Pen2，5]脑啡肽（DPDPE）和[D - Ala2]强啡肽II（DELT），在选择性培育的高（HA）低（LA）游泳应激诱导镇痛（SIA）小鼠中，镇痛效力存在巨大差异。分别为高和低左啡诺镇痛而选择性培育的HAR和LAR小鼠，对DAMGO的镇痛敏感性同样存在巨大差异，对DPDPE的敏感性差异适中，对DELT的敏感性无差异。镇痛效力上这些显著的基因型差异伴随着全脑匀浆中[3H]DPDPE和/或[3H]DELT结合的HA/LA及HAR/LAR差异，但矛盾的是[3H]DAMGO结合无差异。编码μ（MOR - 1）或δ（DOR - 1）阿片受体的mRNA提取物的溶液杂交表明高低品系间基因表达存在一些区域差异。令人惊讶的是，这些体外标志物的差异方向通常是LAR > HAR。目前的数据表明，对SSIA或左啡诺镇痛进行选择会对μ和δ阿片类镇痛产生不同影响，同时伴有体外检测的改变，其意义尚待确定。结合体外生物学标志物和镇痛遗传模型的实用性对数据进行了讨论。
