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KMID : 0811720060100000327
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Korean Journal of Physiology & Pharmacology
2006 Volume.10 No. 0 p.327 ~ p.0
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CHANGES IN GENE EXPRESSION OF SPECIFIC G-PROTEINS AND RGSS SUPPORT POTENTIATION OF MORPHINE ANALGESIA BY ADRENALECTOMY
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Fereshteh Motamedi
Saeed Esmaeili Mahani
Masoud Fereidoni
Abolhasan Ahmadiani
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Abstract
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There are some reports indicating that adrenalectomy significantly potentiates morphine analgesia in low and high doses. Since the G-protein subunits and RGSs have an important role in morphine effects at cellular level and the exact mechanism of adrenactomy-induced morphine sensitization has not been clarified, the present study was designed to determine the changes in the level of Gαi/o, Gαs, Gβ, RGS2 and RGS4 mRNA in this phenomenon. All experiments were carried out on male wistar rats, weighing 200～250 g, and the tail-flick test was used to assess the nociceptive threshold. The dorsal half of the lumbar spinal cord was assayed for the expression of G-proteins and RGSs using semiquantitative PCR normalized to beta-actin gene expression. Results show that morphine not only in 3 mg/kg but also in the sub-effective dose (2 mg/kg) could affect nociceptive threshold and induce analgesic response in adrenalectomized (ADX) rats and the analgesic effect of 2 mg/kg morphine in ADX rats was greater than sham operated animals 30 min after injection (p<0.01). This effect was reversed with corticosterone replacement. Adrenalectomy produced a significant increase in the level of Gi/o (79%), G (96%) and RGS2 (114%) in dorsal portion of lumbar spinal cord. In contrast no significant changes were observed in mRNA level for Gs and RGS4. In sham operated animals, administration of morphine induced significant increase in Gi/o, G and RGS4 gene expression. No significant changes were detected in Gs and RGS2 mRNA levels. In adrenalectomized rats (ADX), injection of morphine caused a significant decrease in G mRNA level compared to saline injected group. There was no change in other genes mRNA. Comparison of the effect of morphine on the levels of G-protein subunits and RGSs mRNA in sham operated and ADX animals revealed that RGS2 mRNA level in ADX animals which treated with morphine is grater than (270%) mRNA
level in sham operated animals. In contrast, RGS4 mRNA level in ADX animals which treated with morphine is lower than (40%) mRNA level in morphine injected sham operated animals. In conclusion, the levels of cellular component involved in morphine analgesia significantly increase in ADX animals, which might be, at least in part, responsible for adrenalectomy-induced morphine sensitization.
Source: Korean J Physiol Pharmacol.2006 Oct;10(Suppl II):239
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KEYWORD
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adrenalectomy, analgesia, G proteins, RGS
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