IRAS, a candidate for I1-imidazoline receptor, mediates inhibitory effect of agmatine on cellular morphine dependence.

Abstract

Agmatine, an endogenous ligand for the I1-imidazoline receptor, has previously been shown to prevent morphine dependence in rats and mice. To investigate the role of imidazoline receptor antisera-selected protein (IRAS), a strong candidate for I1R, in morphine dependence, two CHO cell lines were created, in which mu opioid receptor (MOR) was stably expressed alone (CHO-mu) or MOR and IRAS were stably co-expressed (CHO-mu/IRAS). After 48 h administration of morphine (10 microM), naloxone induced a cAMP overshoot in both cell lines, suggesting cellular morphine dependence had been produced. Agmatine (0.1-2.5 microM) concentration-dependently inhibited the naloxone-precipitated cAMP overshoot when co-pretreated with morphine in CHO-mu/IRAS, but not in CHO-mu. Agmatine at 5-100 microM also inhibited the cAMP overshoot in CHO/mu and CHO-mu/IRAS. Efaroxan, an I1R-preferential antagonist, completely blocked the effect of agmatine on the cAMP overshoot at 0.1-2.5 microM in CHO-mu/IRAS, while partially reversing the effects of agmatine at 5-100 microM. L-type calcium channel blocker nifedipine entirely mimicked the effects of agmatine at high concentrations on forskolin-stimulated cAMP formation in CHO-mu and naloxone-precipitated cAMP overshoot in morphine-pretreated CHO-mu. Therefore, IRAS, in the co-transfected CHO-mu/IRAS cell line, appears necessary for low concentrations of agmatine to cause attenuation of cellular morphine dependence. An additional effect of agmatine at higher concentrations seems to relate to both transfected IRAS and some naive elements in CHO cells, and L-type voltage-gated calcium channels are not ruled out. This study suggests that IRAS mediates agmatine's high affinity effects on cellular morphine dependence and may play a role in opioid dependence.

• Authors: Ning Wu, Rui-Bin Su, Bo Xu, Xin-Qiang Lu, Yin Liu, Jian-Quan Zheng, John E Piletz, Jin Li, Bo-Yi Qin
• Journal: Biochemical pharmacology (Biochem Pharmacol) Vol. 70 Issue 7 Pg. 1079-87 (Oct 01 2005) ISSN: 0006-2952 [Print] England
• PMID: 16112088 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• BU 224
• Imidazoles
• Imidazoline Receptors
• Intracellular Signaling Peptides and Proteins
• NISCH protein, human
• Naloxone
• Dizocilpine Maleate
• Agmatine
• Morphine
• Cyclic AMP
• Nitric Oxide Synthase
• Nifedipine
• NG-Nitroarginine Methyl Ester

Topics

• Agmatine (pharmacology)
• Animals
• CHO Cells
• Cricetinae
• Cyclic AMP (metabolism)
• Dizocilpine Maleate (pharmacology)
• Imidazoles (pharmacology)
• Imidazoline Receptors
• Intracellular Signaling Peptides and Proteins (physiology)
• Morphine (pharmacology)
• NG-Nitroarginine Methyl Ester (pharmacology)
• Naloxone (pharmacology)
• Nifedipine (pharmacology)
• Nitric Oxide Synthase (metabolism)