Opioid receptor exposure

McDowell J, Kitchen I. 1988. Perinatal lead exposure alters the development of 5- but not p-opioid receptors in rat brain. Br J Pharmacol 94 933-937. 

Zhao GM et al Profound spinal tolerance after repeated exposure to a highly selective mu-opioid peptide agonist Role of delta-opioid receptors. J Pharmacol Exp Ther 2002 302 188. [PMID 12065716]... 

House, R.V., Thomas, P.T., Bhargava, H.N. A comparative study of immunmodulation produced, by in vitro exposure to delta opioid receptor agonist peptides, Peptides 1996, 17, 75-81. 

Li Y, Li JJ, Yu LC (2002b) Anti-nociceptive effect of neuropeptide Y in the nucleus accumbens of rats an involvement of opioid receptors in the effect. Brain Res 940 69-78 Liang D, Li X, Lighthall G, Clark JD (2003) Heme oxygenase type 2 modulates behavioral and molecular changes during chronic exposure to morphine. Neuroscience 121 999-1005... 

Tolerance may result from a compensatory biochemical cell response to continued exposure to opioid. In short, both physical dependence and tolerance may follow the operation of homeostatic adaptation to continued high occupancy of opioid receptors. Changes of similar type may occur with GABA transmission, involving benzodiazepines. 

Recent studies have suggested that compounds acting as delta opioid receptor agonists may exhibit immunostimulatory activity. For example, both IL-2 and IL-4 production were markedly enhanced by DPDPE at concentrations between 0.00001 and 0.1 M. Exposure to H-Tyr-D-Thr-Gly-Phe-Leu-Thr-OH (DTEET) and DPDPE was associated with a significant enhancement in NK cell activity. More extensive mechanistic studies are in progress to define the nature of this immunomodulatory activity. 

Several nonpeptide delta opioid receptor antagonists are currently under investigation in this project, including 7-benzylidene-7-dehydronaltrexone HCl (BNTX), naltrindole (NTI), and naltriben (NTB). In vitro exposure to BNTX or NTI results in immunosuppression at concentrations between 0.1 and 10 M, consonant with the hypothesis that delta opioid receptor agonists enhance, but delta receptor antagonists suppress, immune functional parameters. In comparison, in vitro exposure to NTB did not result in any detectable alteration in immune function. 

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