Opioid Peptides Modulates Angiogenesis On CAM And Melatonin Inverses Tolerance Of Del I In Mice

Opioids can produce potent antinociception, but simultaneously also bring many side effects including respiratory depression, nausea, constipation, dependence and tolerance, which greatly limit the clinical application of opioids. To reduce these side effects without disturbing the clinical efficacy, we used opioids together with other pharmacological agents. So in the present, we studied the effect of melatonin on opioid peptides in mice tail-flick test. The results showed that melatonin reduced the tolerance of del I analgesia, but not that of EM-1. The effect was dose dependent. The reversion of melatonin on tolerance of del I analgesia was antagonized by luzindole, a specific inhibitor of MT2 receptor, suggesting that it involved in the MT2 receptor.The endogenous opioids were the neurotransmitter and neuromodulator presented in human and animals widely, they exerted effects in nerve system, endocrine system and immune system, especially in the antinociception and cardiovascular system. We studied the effects of opioids on angiogenesis. The results showed that EM-1, EM-2 and del I increased the area and the number of new blood vessel, and this effect was dose-dependent. Naloxone could antagonize the effects of opioids, which suggested that the effects were modulated by the opioid receptor.Here we also studied the antinociceptive activity of RGD after i.c.v. administration. RGD was found to display potent antinociceptive activity and moved slowly when administrated i.c.v. (5nmol, 15nmol, 45nmol/2.5ul) in mice, which showed a dose-related result. However, naloxone could not reverse the antinociceptive activity, indicating that the antinociception of RGD was not mediated by the opioid system. In addition, RGE, a contrast peptide admininstrated in mice, showed no antinociceptive activity further suggesting that RGD might induced its antinociceptive activity by interacting with integrin.