研究多巴胺受体拮抗剂左旋四氢巴马汀（l2THP）加强电针镇痛（EAA）的原理，阐明中枢神经系统内多巴胺（DA） 系统在EAA中的作用。方法：分别将D1受体激动剂SK&F-38393和D2受体激动剂quinpirole hydrochloride（Qui）注射入大鼠伏膈核，观察对EAA及ι-THP加强EAA的作用。结果：SK&F-38393（5μg，10μg）明显对抗了ι-THP加强EAA的作用，10μgSK&F-38393则减弱EAA；Qui（10μg，20μg）对EAA及ι-THP加强EAA的作用没有显著影响。结论：伏膈核内D1受体活动在EAA及ι-THP加强EAA中起重要作用，D2受体没有显著作用。

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.

[Phe1ψ(CH2-NH) Gly2 nociceptin-(1-13)-NH2, a pseudopeptide analog of nociceptin, was originally seen as an antagonist of nociceptin receptors. In the present study, it was observed that intracerebroventricular (i. c. v.) injection of this pseudopeptide (1, 5, 10μg) significantly decreased the tail-flick latency of rats, indicating a hyperalgesic effect, while intrathecal (i. t.) injection of it (1, 2.5, 10μg) dramatically increased the tail-flick latency, indicating an analgesic effect. This strengthened the in vivo evidence that [Phe1ψ(CH2-NH) Gly2] nociceptin-1-13-NH might be an agonist of nociceptin receptors.

We examined whether expression of monokine induced by IFN-γ(Mig, CXCL9) in tumors could produce antitumor effects. Murine lung carcinoma cells (A11) were retrovirally transduced with the murine Mig gene (A11/Mig) and were inoculated into syngeneic mice. Although proliferation in vitro of A11/Mig cells was not different from that of parent cells, the growth in vivo of A11/Mig tumors was significantly retarded compared with that of parent tumors. The antitumor effect was dependent on the amount of Mig produced. We compared the expression level of marker genes of lymphocytes and endothelial cells between parent and A11/Mig tumor masses with reverse transcription-polymerase chain reaction. Expression of CD4, CD8α, CD40, CD86, CD28, CD31 and vascular endothelial growth factor was not different between the two tumor groups but expression of CD40 ligand, CD80, NK1.1 and CXCR3 was relatively lower in A11/Mig tumors. Although Mig is a chemotactic factor for activated T and NK cells and an inhibitor for angiogenesis, the present data suggested that production of Mig in tumors did not recruit activated T and NK cells efficiently or suppress angiogenesis. The antitumor effects by Mig could be independent of anti-angiogenesis and recruitment of T and NK cells.