Effects of morphine glucuronides on the function of opioid receptors in human SK-N-SH cells

Morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) are active me tabolites of morphine. The effects of M3G and M6G on the opioid receptor tr ansduction system has not yet been fully elucidated. Formation of cAMP afte r treatment with various doses of morphine, M3G, and M6G was studied. M6G a nd morphine, but not M3G, showed a dose dependent inhibition of cAMP accumu lation. Naloxone blocked the inhibitory effect of M6G, M3G, and morphine. P retreatment with M3G did not change the effects of morphine and M6G, The G- protein inhibitor PTX, prevented morphine, M3G, and M6G effects on cAMP. M3 G and M6G vary in their ability to interact with the opioid receptor effect or system. Inhibition of cAMP evoked by activation of opioid receptors and inhibitory G-proteins may play a role in the actions of M6G and M3G. (C) 20 00 Elsevier Science Ireland Ltd. All rights reserved.