Meunier J C, Mollereau C, Toll L, Suaudeau C, Moisand C, Alvinerie P, Butour J L, Guillemot J C, Ferrara P, Monsarrat B
Laboratoire de Pharmacologie et de Toxicologie Fondamentales, CNRS UPR 8221, Toulouse, France.
Nature. 1995 Oct 12;377(6549):532-5. doi: 10.1038/377532a0.
The ORL1 receptor, an orphan receptor whose human and murine complementary DNAs have recently been characterized, structurally resembles opioid receptors and is negatively coupled with adenylate cyclase. ORL1 transcripts are particularly abundant in the central nervous system. Here we report the isolation, on the basis of its ability to inhibit the cyclase in a stable recombinant CHO(ORL1+) cell line, of a neuropeptide that resembles dynorphin A9 and whose amino acid sequence is Phe-Gly-Gly-Phe-Thr-Gly-Ala-Arg-Lys-Ser-Ala-Arg-Lys-Leu-Ala-Asn-Gln. The rat-brain cDNA encodes the peptide flanked by Lys-Arg proteolytic cleavage motifs. The synthetic heptadecapeptide potently inhibits adenylate cyclase in CHO(ORL1+) cells in culture and induces hyperalgesia when administered intracerebroventricularly to mice. Taken together, these data indicate that the newly discovered heptadecapeptide is an endogenous agonist of the ORL1 receptor and that it may be endowed with pro-nociceptive properties.
孤啡肽受体（ORL1受体）是一种孤儿受体，其人类和鼠类互补DNA最近已被鉴定。它在结构上类似于阿片受体，并与腺苷酸环化酶负偶联。ORL1转录本在中枢神经系统中特别丰富。在此，我们报告了一种神经肽的分离，该神经肽基于其在稳定的重组CHO（ORL1 +）细胞系中抑制环化酶的能力而被分离出来。它类似于强啡肽A9，其氨基酸序列为Phe-Gly-Gly-Phe-Thr-Gly-Ala-Arg-Lys-Ser-Ala-Arg-Lys-Leu-Ala-Asn-Gln。大鼠脑cDNA编码的肽两侧是Lys-Arg蛋白水解切割基序。合成的十七肽在培养的CHO（ORL1 +）细胞中有效抑制腺苷酸环化酶，并在向小鼠脑室内给药时诱导痛觉过敏。综上所述，这些数据表明新发现的十七肽是ORL1受体的内源性激动剂，并且它可能具有促伤害感受特性。
