Elsevier

Life Sciences

Volume 45, Issue 20, 1989, Pages 1937-1942
Life Sciences

Morphine-induced desensitization and down-regulation at mu-receptors in 7315c pituitary tumor cells

https://doi.org/10.1016/0024-3205(89)90548-1Get rights and content

Abstract

Pituitary 7315c tumor cells maintained in culture were treated with varying concentrations of morphine from 10 nM to 300 μM, for periods of five or forty-eight hours. The ability of the mu-opioid receptor agonist, DAMGO, to inhibit forskolin-stimulated adenylyl cyclase in washed membrane preparations from the treated cells was compared with its activity in membranes from cells incubated in the absence of added morphine. In the same membrane preparations, the number and affinity of mu-opioid receptors was estimated by measurements of [3H]diprenorphine binding. After 5 hr of treatment with morphine concentrations of 100 nM or higher, a significant reduction in inhibition of adenylyl cyclase by DAMGO was observed. Little further loss of agonist activity was observed when the incubations were extended to 48 hr. After 5 hr of morphine treatment, there was no change in either the number of receptors, or their affinity for [3H]diprenorphine. However, after 48 hr of morphine treatment, greater than 25% reductions in receptor number were apparent with morphine pretreatment concentrations of 10 μM or higher. These results suggest that opioid tolerance in this system is primarily associated with a reduced ability of agonist-occupied receptor to activate the effector system. Receptor down-regulation was not necessary for loss of agonist response, although a reduction in receptor number occurred after exposure to high concentrations of morphine for periods longer than 5 hr.

References (9)

  • P.J. Munson et al.

    Analyt. Biochem.

    (1980)
  • D.L. Aub et al.

    J. Biol. Chem.

    (1986)
  • J. Magnan et al.

    Naunyn-Schmiedebergs Arch. Pharmacol.

    (1982)
  • P.Y. Law et al.

    Mol. Pharmacol.

    (1983)
There are more references available in the full text version of this article.

Cited by (68)

  • Key differences in regulation of opioid receptors localized to presynaptic terminals compared to somas: Relevance for novel therapeutics

    2023, Neuropharmacology
    Citation Excerpt :

    Since all vlPAG neurons express NOP, NOP agonists directly inhibit vlPAG-RVM output neurons, thus negating actions of opioids on the circuit. Activation of NOP receptors with N/OFQ produces rapid desensitization (Pennock et al., 2012; Pu et al., 1999) and robust receptor internalization (Baiula et al., 2013; Corbani et al., 2004; Donica et al., 2013; Spampinato and Baiula, 2006; Spampinato et al., 2001, 2007). Phosphorylation of NOP by GRK3 results in desensitization, β-arrestin2-recruitment, internalization and arrestin-dependent JNK MAPK signaling (Hawes et al., 1998; Zhang et al., 2012).

  • Evaluating the expression pattern of the opioid receptor in pituitary neuroendocrine tumors (PitNET) and the role of morphine and naloxone in the regulation of pituitary cell line growth and apoptosis

    2023, Biomedicine and Pharmacotherapy
    Citation Excerpt :

    Notably, concentrations of 0.001–10 µM morphine had no significant effect on GH3 pituitary cell proliferation and survival (data not shown). Regarding the possible effect of morphine on MOR in pituitary tumor cells, a study has shown that concentrations greater than 10 µM morphine can decrease the number of opioid receptors and desensitization [44]. Based on our data, the opioid receptor appeared to be involved in morphine-induced GH3 cell death, however, the aim of this study was not to assess the number of MOR after morphine administration.

  • Chronic morphine treatment up-regulates mu opioid receptor binding in cells lacking filamin A

    2007, Brain Research
    Citation Excerpt :

    Extensive studies in many different cell lines demonstrated MOP down-regulation by different agonists (Baumhaker et al., 1993; Chakrabarti et al., 1995; Kato et al., 1998; Yabaluri and Medzihradsky, 1997). Chronic morphine-induced MOP down-regulation has been well investigated and characterized in a various cell culture systems, such as SH-SY5Y (Zadina et al., 1993), HEK (Onoprishvili et al., 1999), CHO (Kato et al., 1998), C6 (Yabaluri and Medzihradsky, 1997), Neuro2a (Chakrabarti et al., 1995), 7315c (only 20%) (Puttfarcken and Cox, 1989) and SK-N-SH (Baumhaker et al., 1993). Opioid receptor up-regulation by antagonist treatment is a well-established phenomenon in animals and cell cultures.

  • Internalization and down-regulation of mu opioid receptors by endomorphins and morphine in SH-SY5Y human neuroblastoma cells

    2004, Brain Research
    Citation Excerpt :

    By contrast, the mu opioid receptor has been shown in several systems to be resistant to internalization by morphine [1,8,29,45]. Nevertheless, morphine can induce down-regulation of the mu opioid receptor [4–6,28,42,57,59]. There are several studies that indicate a dissociation between GPCR internalization and down-regulation.

View all citing articles on Scopus

Present address: Department of Psychiatry, Meyer 4–163, Johns Hopkins University, School of Medicine, 600 N. Wolfe Street, Baltimore, MD 21205.

View full text