Opioid receptor like 1 (ORL1) receptor is a novel member of the opioid receptor family, which was not bound by any of the typical opioid receptor ligands but bound by the recently discovered nociceptin (also termed orphanin FQ) with high af

DNA polymerase κ (POLκ) is a low fidelity translesional DNA polymerase implicated in spontaneous and DNA damage-induced mutagenesis. We have previously shown that POLκ was frequently overexpressed in human lung cancer tissues as compared with their matched nontumorous tissue counterpart. In the present study, we found a close correlation between elevated POLκ expression and p53 inactivation in lung cancer tissues. To investigate whether POLK expression might be regulated by p53, we have determined the transcriptional initiation site of POLK gene and examined its promoter activity in A549, H358-129, and PC-3 human lung cancer cell lines. Wild-type p53, but not a mutant p53 (R273H) devoid of the DNA-binding activity, strongly inhibited POLK promoter activity in these cells. In addition, POLK promoter exhibited a significantly higher activity in p53-/- murine embryo fibroblasts (MEF) than in p53+√- and p53+√+ MEF. These results link p53 status with POLκ expression and suggest that loss of p53 function may in part contribute to the observed POLκ upregulation in human lung cancers.

Orphanin FQ (also known as nociceptin) is a 17-amino-acid peptide which acts as a potent endogenous agonist of the orphan opioid receptor-like (ORL1) receptor. Endomorphin-1, a 4-amino-acid peptide discovered recently, is a potent and selective endogenous agonist for the m-opiate receptor. In the present study, the effect of OFQ orrand endomorphin-1 on the response to noxious thermal stimuli was observed using the tail-flick test in rats. Intracerebroventricular (i. c. v.) administration of OFQ (1,5μg) could shorten tail-flick latency; In contrast, intrathecal (i. t.) administration of OFQ (1, 2 or 10μg) could increase the latency; i. c. v. (1, 2, 5μg) or i. t. (0.2, 2, 5μg) administration of endomorphin-1 dose-dependently increased the latency, indicating an analgesic effect. Furthermore, OFQ (0.1-5μg) when intraventricularly injected together with endomorphin-1 (5μg), could dose-dependently reverse the analgesia induced by the latter. On the contrary, OFQ (1μg) intrathecally injected together with endomorphin-1 (0.2μg) could further increase the tail-flick latency. The results showed that OFQ at the supraspinal level produces hyperalgesia and is antagonistic to endomorphin-1, while at the spinal level it produces analgesia and is synergic with endomorphin-1. Different interaction mechanism between OFQ and endomorphin-1 in the brain and the spinal cord is thus suggested. © 1999 Elsevier Science B. V. All rights reserved.