Rossi G C, Pan Y X, Brown G P, Pasternak G W
George C. Cotzias Laboratory of Neuro-Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
FEBS Lett. 1995 Aug 7;369(2-3):192-6. doi: 10.1016/0014-5793(95)00757-z.
Although MOR-1 encodes a mu opioid receptor, its relationship to the pharmacologically defined mu receptor subtypes has been unclear. Antisense mapping now suggests that these subtypes result from alternative splicing of MOR-1. Three oligodeoxynucleotide probes targeting exon 1 and another oligodeoxynucleotide directed against the coding region of exon 4 block supraspinal morphine analgesia, a mu1 action, while five of six oligodeoxynucleotides directed against exons 2 and 3 are inactive. Inhibition of gastrointestinal transit and spinal morphine analgesia, two mu2 actions, are blocked only by the probe against exon 4 and not by those directed against exon 1. In contrast, the analgesic actions of the extraordinarily potent mu drug morphine-6 beta-glucuronide are blocked by six different antisense oligodeoxynucleotides targeting exons 2 and 3, but not by those acting on exons 1 or 4. These results suggest that the mu1 and mu2 receptor subtypes originally defined in binding and pharmacological studies result from alternative splicing of MOR-1 while morphine-6 beta-glucuronide acts through a novel, previously unidentified receptor which is yet another MOR-1 splice variant.
尽管MOR-1编码一种μ阿片受体，但其与药理学定义的μ受体亚型之间的关系尚不清楚。反义图谱现在表明，这些亚型是由MOR-1的可变剪接产生的。三种靶向第1外显子的寡脱氧核苷酸探针和另一种针对第4外显子编码区的寡脱氧核苷酸可阻断脊髓上吗啡镇痛，这是一种μ1作用，而针对第2和第3外显子的六种寡脱氧核苷酸中的五种则无活性。抑制胃肠蠕动和脊髓吗啡镇痛，这两种μ2作用，仅被针对第4外显子的探针阻断，而不被针对第1外显子的探针阻断。相比之下，极其强效的μ药物吗啡-6β-葡萄糖醛酸的镇痛作用被六种靶向第2和第3外显子的不同反义寡脱氧核苷酸阻断，但不被作用于第1或第4外显子的那些阻断。这些结果表明，最初在结合和药理学研究中定义的μ1和μ2受体亚型是由MOR-1的可变剪接产生的，而吗啡-6β-葡萄糖醛酸通过一种新的、以前未鉴定的受体起作用，该受体是MOR-1的另一种剪接变体。
