Effects of Whole Body Irradiation on Morphine, DAMGO, DPDPE, U50,488H and $\beta$-endorphin-Induced Antinociception

  • Park, Tae-Won (Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute) ;
  • Kim, Jin-Kyu (Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute) ;
  • Jeong, Jae-Soo (LG Household & Health Care Ltd.) ;
  • Kim, Tae-Wan (Department of Veterinary Physiology, College of Veterninary Medicine, Kyungpook National University) ;
  • Cho, Young-Kyung (Department of Physiology and Neuroscience, College of Dentistry and Research Institute of Oral Biology, Gangneung-Wonju National University) ;
  • Kim, Kyung-Nyun (Department of Physiology and Neuroscience, College of Dentistry and Research Institute of Oral Biology, Gangneung-Wonju National University) ;
  • Chung, Ki-Myung (Department of Physiology and Neuroscience, College of Dentistry and Research Institute of Oral Biology, Gangneung-Wonju National University)
  • 투고 : 2011.12.05
  • 심사 : 2012.02.14
  • 발행 : 2012.03.31

초록

Opioid receptors have been pharmacologically classified as ${\mu}$, ${\delta}$, ${\kappa}$ and ${\varepsilon}$. We have recently reported that the antinociceptive effect of morphine (a ${\mu}$-opioid receptor agonist), but not that of ${\beta}$-endorphin (a novel ${\mu}/{\varepsilon}$-opioid receptor agonist), is attenuated by whole body irradiation (WBI). It is unclear at present whether WBI has differential effects on the antinociceptive effects of ${\mu}-$, ${\delta}-$, ${\kappa}-$ and ${\varepsilon}$-opioid receptor agonists. In our current experiments, male ICR mice were exposed to WBI (5Gy) from a $^{60}Co$ gamma-source and the antinociceptive effects of opioid receptor agonists were assessed two hours later using the hot water ($52^{\circ}C$) tail-immersion test. Morphine and $D-Ala^2$, $N-Me-Phe^4$, Gly-olenkephalin (DAMGO), [$D-Pen^2-D-Pen^5$] enkephalin (DPDPE), trans-3,4-Dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]-benzeneacetamide (U50,488H), and ${\beta}$-endorphin were tested as agonists for ${\mu}$, ${\delta}$, ${\kappa}$, and ${\varepsilon}$-opioid receptors, respectively. WBI significantly attenuated the antinociceptive effects of morphine and DAMGO, but increased those of ${\beta}$-endorphin. The antinociceptive effects of DPDPE and U50,488H were not affected by WBI. In addition, to more preciously understand the differential effects of WBI on ${\mu}-$ and ${\varepsilon}$-opioid receptor agonists, we assessed pretreatment effects of ${\beta}$-funaltrexamine (${\beta}$-FNA, a ${\mu}$-opioid receptor antagonist) or ${\beta}$-$endorphin_{1-27}$ (${\beta}$-$EP_{1-27}$, an ${\varepsilon}$-opioid receptor antagonist), and found that pretreatment with ${\beta}$-FNA significantly attenuated the antinociceptive effects of morphine and ${\beta}$-endorphin by WBI. ${\beta}$-$EP_{1-27}$ significantly reversed the attenuation of morphine by WBI and significantly attenuated the increased effects of ${\beta}$-endorphin by WBI. The results demonstrate differential sensitivities of opioid receptors to WBI, especially for ${\mu}-$ and ${\varepsilon}$-opioid receptors.

키워드

참고문헌

  1. Feinendegen LE. Evidence from beneficial low level radiation effects and radiation hormesis. Br J Radiol. 2005; 78:3-7.
  2. Mickley GA, Stevens KE, White GA, Gibbs GL. Changes in morphine self-administration after exposure to ionizing radiation: evidence for the involvement of endorphins. Life Sci. 1984;33:711-8.
  3. Teskey CC, Kavaliers M. Ionizing radiation induces opioidmediated analgesia in male mice. Life Sci. 1984;35:1547-52.
  4. Raffa RB, Mathiasen JR, Brown DQ. ${\mu}$-, but not ${\delta}$-, opioid receptor-mediated antinociception in mice is attenuated by ${\gamma}$-irradiation. Brain Res. 1988;447(2):393-7.
  5. Contet C, Matifas A, Kieffer BL. No evidence for G-proteincoupled epsilon receptor in the brain of triple opioid receptor knockout mouse. Eur J Pharmacol. 2004;492:131-6.
  6. Jung JS, Song DK, Suh HW, Kim YH. Effects of intraventricular injection of morphine and beta-endorphin on serotonin release from the spinal cord in rats. Pharmacol Biochem Behav. 1994;49(4):1037-424.
  7. Suh HH, Fujimoto JM, Tseng LF. Differential mechanisms mediating beta-endorphin- and morphine-induced analgesia in mice. Eur J Pharmacol. 1989;168(1):61-70.
  8. Chung KM, Suh HW. Pretreatment with cholera or pertussis toxin differentially modulates morphine- and betaendorphin- induced antinociception in the mouse formalin test. Neuropeptides. 2001;35(5-6):197-203.
  9. Narita M, Tseng LF. Evidence for the existence of the ${\beta}$- endorphin-sensitive "epsilon opioid receptor" in the brain: the mechanisms of epsilon-mediated antinociception. Jpn J Pharmacol. 1998;76:233-53.
  10. Tseng LF. Evidence for epsilon opioid receptor-mediated ${\beta}$- endorphin-induced analgesia. Trends Pharmacol Sci. 2001; 22: 623-30.
  11. Seo YG, Kwon MS, Choi HW, Jang JE, Lee JK, Jung JS, Park SH, Suh HW. The differential effect of morphine and beta-endorphin administered intracerebroventricularly on pERK and pCaMK-II expression induced by various nociceptive stimuli in mice brains. Neuropeptides. 2008; 42(3):319-30.
  12. Mizoguchi H, Narita M, Nagase H, Tseng LF. Activation of G-proteins in the mouse pons/medulla by ${\beta}$-endorphin is mediated by the stimulation of ${\mu}$- and putative ${\varepsilon}$- receptors. Life Sci. 2000;67:2733-43.
  13. Kim DK, Kim CS, Kim HJ, Kook JK, Kim SH, Lee BH, Lee YH, Mo SY, Loh HH. The effect of morphine on rest expression in human neuroblastoma NMB cells. Int J Oral Biol. 2010;35(2):69-74.
  14. Kim KN, Chung KM. The differential effect of whole-body irradiation on morphine- and ${\beta}$-endorphin-induced antinociceptive actions in mice. Int J Oral Biol. 2009;34(3): 137-42.
  15. Chung KM, Jung YK, Jeong HY, Kim KN. Differential involvement of glutathione in morphine and ${\beta}$-endorphin induced antinociception in male ICR mice. Int J Oral Biol. 2003;28(2):33-7.
  16. Ben-Bassat J, Peretz E, Sulman FG. Analgesimetry and ranking of analgesic drugs by the receptacle method. Arch Int Pharmacodyn Ther. 1959;122:434-47.
  17. Haley TJ, McCormick WG. Pharmacological effect of produced by intracerebral injections of drugs in the conscious mouse. Br J Pharmacol. 1957;12:12-5.
  18. Hong M, Sutak M, Jhamandas K. Inhibition of spinal opioid antinociception by intrathecal ${\beta}-endorphin_{1-27}$ in the rat. Br J Pharmacol. 1993;108:1137-42.
  19. Ju JS, Choi HS, Lee HJ, Jung CY, Lee KR, Bae YC, Ahn DK. Microinjection of DAMGO but not DPDPE or U50488 into the central nucleus of amygdala suppressed nociceptive jaw opening reflex in freely moving rats. Int J Oral Biol. 2004; 29(2):45-9.
  20. Wuster M, Schulz R, Herz A. Specificity of opioids towards the mu, delta and epsilon opiate receptors. Neurosci Lett. 1979;15:193-8.
  21. Mizoguchi H, Wu HE, Narita M, Hall FS, Sora I, Uhl GR, Nagase H, Tseng LF. Antagonistic property of buprenorphine for putative epsilon opioid receptor-mediated G-protein activation by ${\beta}$-endorphin in pons/medulla of the mu opioid receptor knockout mouse. Neuroscience. 2002;115:715-21.
  22. Gilmore W, Weiner LP. The opioid specificity of ${\beta}$-endorphin enhancement of murine lymphocyte proliferation. Immunopharmacology 1989;17:19-30.
  23. George SR, Fan T, Xie Z, Tse R, Tam V, Varghese G, O'Dowd BF. Oligomerization of mu and delta opioid receptors. Generation of novel functional properties. J Biol Chem. 2000;275:26128-35.
  24. Katanyutanon S, Wu R, Wang P. The effect of whole-body radiation on blood levels of gastrointestinal peptides in the rat. Int J Clin Exp Med. 2008;1:332-7.