Effects of Whole Body Irradiation on Morphine, DAMGO, DPDPE, U50,488H and β-endorphin-Induced Antinociception
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Opioid receptors have been pharmacologically classified as μ, δ, κ and ε. We have recently reported that the antinociceptive effect of morphine (a μ-opioid receptor agonist), but not that of β-endorphin (a novel μ/ε-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 μ-, δ-, κ- and ε-opioid receptor agonists. In our current experiments, male ICR mice were exposed to WBI (5Gy) from a 60Co gamma-source and the antinociceptive effects of opioid receptor agonists were assessed two hours later using the hot water (52o C) tailimmersion 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 β-endorphin were tested as agonists for μ, δ, κ, and ε-opioid receptors, respectively. WBI significantly attenuated the antinociceptive effects of morphine and DAMGO, but increased those of β-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 μ- and ε-opioid receptor agonists, we assessed pretreatment effects of β-funaltrexamine (β-FNA, a μ-opioid receptor antagonist)or β-endorphin1-27 (β-EP1-27, an ε-opioid receptor antagonist),and found that pretreatment with β-FNA significantly attenuated the antinociceptive effects of morphine and β-endorphin by WBI. β-EP1-27 significantly reversed the attenuation of morphine by WBI and significantly attenuated the increased effects of β-endorphin by WBI. The results demonstrate differential sensitivities of opioid receptors to WBI, especially for μ- and ε-opioid receptors.
Abstract
Opioid receptors have been pharmacologically classified as μ, δ, κ and ε. We have recently reported that the antinociceptive effect of morphine (a μ-opioid receptor agonist), but not that of β-endorphin (a novel μ/ε-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 μ-, δ-, κ- and ε-opioid receptor agonists. In our current experiments, male ICR mice were exposed to WBI (5Gy) from a 60Co gamma-source and the antinociceptive effects of opioid receptor agonists were assessed two hours later using the hot water (52o C) tailimmersion 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 β-endorphin were tested as agonists for μ, δ, κ, and ε-opioid receptors, respectively. WBI significantly attenuated the antinociceptive effects of morphine and DAMGO, but increased those of β-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 μ- and ε-opioid receptor agonists, we assessed pretreatment effects of β-funaltrexamine (β-FNA, a μ-opioid receptor antagonist)or β-endorphin1-27 (β-EP1-27, an ε-opioid receptor antagonist),and found that pretreatment with β-FNA significantly attenuated the antinociceptive effects of morphine and β-endorphin by WBI. β-EP1-27 significantly reversed the attenuation of morphine by WBI and significantly attenuated the increased effects of β-endorphin by WBI. The results demonstrate differential sensitivities of opioid receptors to WBI, especially for μ- and ε-opioid receptors.
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