Magnitude of tolerance to fentanyl is independent of μ-opioid receptor density

Chan, Ka Wa; Duttory, Alokesh; Yoburn, Byron C.

doi:10.1016/s0014-2999(96)00960-0

Cited by 16 publications

(2 citation statements)

References 14 publications

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“…Some of the discrepancies may be caused by uncontrolled variables (e.g., different opioids, doses, methods of opioid treatments, anatomical regions, and times samples were taken, integrality of tissue samples before assays, and opioid receptor subtypes studied), as well as detection methods. It has been suggested that MOR down-regulation is agonist selective and depends on the agonist’s intrinsic efficacy (Nishino et al, 1990; Chakrabarti et al, 1997; Chan et al, 1997; Koch and Hollt, 2008). The purity and selectivity of radiolabeled ligands – a problem not only for some early studies, but also in more recent reports employing questionable materials – used in studies are the other potential culprits for conflicting findings.…”

Section: Mu Opioid Receptor and Opioid Tolerancementioning

confidence: 99%

Let-7 microRNAs and Opioid Tolerance

Wang¹

2012

Front. Gene.

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This chapter will focus on the role of microRNAs (miRs) in regulating the actions of opioid drugs through the opioid receptors. Opioids, such as morphine, are analgesics that are used for treating many forms of acute and chronic pain. However, their chronic use is limited by undesirable effects such as opioid tolerance. The μ opioid receptor (MOR) is the primary receptor responsible for opioids’ analgesia and antinociceptive tolerance. The long 3′-untranslated region (3′-UTR) of MOR mRNA is of great interest since this region may contain elements for the post-transcriptional regulation of receptor expression, such as altering the stability of mRNA, influencing translational efficiency, and controlling mRNA transport. MicroRNAs are small non-coding RNA molecules that exert their functions through base-pairing with partially complementary sequences in the 3′-UTR of target mRNAs, resulting in decreased polypeptide formation from those mRNAs. Since the discovery of the first miR, lin-4 in Caenorhabditis elegans, hundreds of miRs have been identified from humans to viruses, which have provided a crucial and pervasive layer of post-transcriptional gene regulation. The nervous system is a rich source of miR expression, with a diversity of miR functions in fundamental neurobiological processes including neuronal development, plasticity, metabolism, and apoptosis. Recently, the let-7 family of miRs is found to be a critical regulator of MOR function in opioid tolerance. Let-7 is the first identified human miR. Its family members are highly conserved across species in sequence and function. In the review, we will present a brief review of the opioid receptors, their regulation, and opioid tolerance as well as an overview of miRs and a perspective how miRs may interact with MOR and serve as a regulator of opioid tolerance.

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Section: Mu Opioid Receptor and Opioid Tolerancementioning

confidence: 99%

Let-7 microRNAs and Opioid Tolerance

Wang¹

2012

Front. Gene.

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“…In morphine-tolerant ilea, the dose of ␤-chlornaltrexamine needed to reduce maximum effects of normorphine is 10-fold lower than that required in nontolerant ilea Goldstein, 1982, 1984). Similarly, clocinnamox and fentanyl infusions produce additive reductions in fentanyl potency in vivo in mice (Chan et al, 1997).…”

mentioning

confidence: 94%

Clocinnamox Distinguishes Opioid Agonists According to Relative Efficacy in Normal and Morphine-Treated Rats Trained to Discriminate Morphine

Walker

Young²

2002

J Pharmacol Exp Ther

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High doses of insurmountable antagonists or frequent administration of high doses of agonists are required to alter the potency of opioid agonists to produce discriminative stimuli. In the present study, insurmountable antagonism and repeated agonist treatment were combined to remove or disable a large enough proportion of -opioid receptors to alter the potency or maximal effect for four agonists in male Sprague-Dawley rats trained to discriminate 3.2 mg/kg morphine from saline under a fixed-ratio 15 schedule of food reinforcement. All agonists produced 88 to 100% morphine responding and were differentially sensitive to clocinnamox antagonism (fentanyl Ͻ morphine Յ buprenorphine ϭ nalbuphine). Repeated treatment with 20 mg/kg per day morphine for 6 days decreased by 2-to 3-fold the potency of fentanyl, morphine, and buprenorphine to produce morphine responding. After morphine treatment, 3.2 mg/kg clocinnamox produced a 7-fold further decrease in morphine potency. Clocinnamox (10 mg/kg) produced a 7-and 12-fold further decrease in morphine and fentanyl potency, respectively, a reduction in the slope of the morphine doseresponse curve, and a suppression of the maximal morphine responding for buprenorphine. Repeated treatment with 10 mg/kg per day morphine for 6 days failed to alter the potency of nalbuphine to produce morphine responding. In these morphine-treated rats, doses of 3.2 or 10 mg/kg clocinnamox suppressed the maximal morphine responding. Taken together, these data indicate that combined insurmountable antagonist and repeated agonist treatment produce additive effects at -opioid receptors to diminish discriminative stimulus effects in a manner predicted by the relative efficacy of opioid agonists.

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Opioid Receptor Signaling and Regulation

Law¹,

Loh²

2006

Handbook of Neurochemistry and Molecular Neurobiology

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Magnitude of tolerance to fentanyl is independent of μ-opioid receptor density

Cited by 16 publications

References 14 publications

Let-7 microRNAs and Opioid Tolerance

Let-7 microRNAs and Opioid Tolerance

Clocinnamox Distinguishes Opioid Agonists According to Relative Efficacy in Normal and Morphine-Treated Rats Trained to Discriminate Morphine

Opioid Receptor Signaling and Regulation

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