The interaction of the mu-opioid receptor and G protein is altered after chronic morphine treatment in rats

1993 ◽  
Vol 348 (5) ◽  
Author(s):  
Pao-Luh Tao ◽  
Chia-Rong Lee ◽  
Ping-Yee Law ◽  
HoraceH. Loh
Keyword(s):  
G Protein ◽  
Opioid Receptor ◽  
Mu Opioid Receptor ◽  
Morphine Treatment ◽  
Chronic Morphine ◽  
Mu Opioid ◽  
Chronic Morphine Treatment

Some effects of putative G-protein biased mu-opioid receptor agonists in male rhesus monkeys

2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Jeremy C. Cornelissen ◽  
Bruce E. Blough ◽  
Laura M. Bohn ◽  
S. Stevens Negus ◽  
Matthew L. Banks
Keyword(s):  
G Protein ◽  
Opioid Receptor ◽  
Rhesus Monkeys ◽  
Mu Opioid Receptor ◽  
Mu Opioid ◽  
Receptor Agonists ◽  
Opioid Receptor Agonists ◽  
Male Rhesus

Subpopulation of Dorsal Horn Neurons Displays Enhanced N -methyl-d-aspartate Receptor Function after Chronic Morphine Exposure

2006 ◽  
Vol 104 (4) ◽  
pp. 815-825 ◽  
Author(s):  
Min Zhao ◽  
Daisy Therese Joo
Keyword(s):  
Nmda Receptor ◽  
Dorsal Horn ◽  
Mu Opioid Receptor ◽  
Receptor Function ◽  
Morphine Treatment ◽  
High Concentration ◽  
Chronic Morphine ◽  
Mu Opioid ◽  
Dorsal Horn Neurons ◽  
Receptor Inhibitor

Background Morphine tolerance may be attributed to enhancement of glutamatergic neurotransmission, in particular to increased function of the N-methyl-D-aspartate (NMDA) receptor. The cellular mechanisms responsible for these changes remain poorly defined. The authors identified and characterized a specific subpopulation of dorsal horn neurons, displaying NMDA receptor plasticity in response to chronic morphine administration. Methods The authors undertook current clamped and voltage clamped recordings of NMDA receptor-mediated responses from cultured rat dorsal horn neurons that were untreated or treated for 7 days with 1 or 100 microm morphine. Results Smaller (capacitance < or = 22 pF), tonic firing neurons showed a significantly enhanced NMDA receptor-mediated peak current after prolonged morphine treatment, whereas larger and phasic firing neurons showed no enhancement. With high-concentration but not low-concentration morphine treatment, Mg2+ blockade of NMDA receptors at resting membrane potentials was reduced. Furthermore, the chronic opioid-induced increase in NMDA current was attenuated by pretreatment with either a mu-opioid receptor inhibitor (naloxone) or an NMDA receptor inhibitor (2-amino-5-phosphonovalerate) (low-concentration > high-concentration morphine). Conclusions In an electrophysiologically defined subpopulation of dorsal horn neurons, enhanced NMDA receptor function after chronic morphine exposure was shown to be mechanistically dependent on morphine concentration and sensitive to both NMDA and mu-opioid receptor antagonism. Therefore, these changes observed in this population of sensory spinal neurons can be used to study the development and prevention of opioid tolerance described in multiple laboratory and clinical reports.

Morphine Stimulates Wound Healing Via Mu Opioid Receptor and Promotes Wound Closure in Sickle Mice

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2118-2118 ◽  
Author(s):  
Derek Vang ◽  
Marna Ericson ◽  
Michael A Ansonoff ◽  
John E Pintar ◽  
Robert P Hebbel ◽  
...  
Keyword(s):  
Wound Healing ◽  
Opioid Receptor ◽  
Vascular Function ◽  
Neurogenic Inflammation ◽  
Wound Closure ◽  
Healing Process ◽  
Mu Opioid Receptor ◽  
Dorsal Skin ◽  
Morphine Treatment ◽  
Mu Opioid

Abstract Abstract 2118 Painful non-healing leg ulcers in sickle cell disease (SCD) pose major treatment challenges for which there is no satisfactory therapy. We observed that the vascular and nerve architecture are abnormal, and mu opioid receptor (MOR) expression is decreased in the skin of BERK mice expressing sickle hemoglobin, as compared to HbA-BERK mice expressing normal human hemoglobin (Kohli et al., Blood, 2010). MOR mediates morphine-induced angiogenesis and analgesia, which are critical to the healing process. We hypothesized that MOR mediates the healing process and that MOR agonists such as morphine will promote healing by stimulating angiogenesis. Ischemic wounds (6 mm diameter) with impaired blood supply were created on the dorsal skin of sickle (BERK, and S+SAntilles) and control (HbA-BERK and C57BL6, respectively) mice; and mu-, delta-, and kappa-opioid receptor knockout (MOR-, DOR- and KOR-KO, respectively) mice and their 129S6 wild type controls. BERK and S+SAntilles did not survive ischemic wound surgery, but S+SAntilles survived non-ischemic, 4 mm punch biopsies on the leg. Wounds were treated topically twice a day with morphine, 3 mg/g Eucerin cream or with PBS-Eucerin cream. Periodic wound tracings were used to quantitate wound area with Adobe Photoshop and % area healed was calculated. Ischemic wounds (100% closure on d17 in control 129S6) took significantly longer to heal as compared to punch biopsies (100% closure on d8 in control C57BL6). Morphine significantly accelerated healing as compared to PBS-cream in control, S+SAntilles, DOR- and KOR-KO, but not in MOR-KO mice, suggesting that morphine-induced healing is MOR-dependent. Of note, PBS-treated ischemic wounds in MOR-KO healed significantly slower than 129S6 control wounds, indicating that MOR is involved in wound healing. Blood flow was significantly higher in the intact unwounded dorsal skin of MOR-KO as compared to 129S6 mice (p<0.001). Significant decrease occurred after wounding in both 129S6 and MOR-KO, which was restored to baseline in morphine-treated 129S6 but not in MOR-KO wounds on d20. Thus, morphine promotes vascular function, which appears to be mediated by MOR in the healing wounds. In PBS-cream treated punch biopsy wounds, 100% wound closure occurred on day 8 as compared to day 6 with morphine treatment in both C57BL6 control and S+SAntilles sickle mice. Laser scanning confocal microscopy (LSCM) of healed wound scars 30d after wounding revealed significantly increased blood vessels (∼2-fold) in morphine-treated as compared to PBS treated in both C57BL6 and S+SAntilles mice. A significant increase was also noted in PGP 9.5-immunoreactive (ir) nerve fibers and lymphatics in morphine-treated scars. Pro-inflammatory and vaso-active neuropeptides, substance P (SP) and calcitonin gene related peptide (CGRP) were increased ∼2-fold in PBS-treated wound scars 30d post-wounding as compared to baseline in S+SAntilles mice, suggestive of increased neurogenic inflammation. However both neuropeptides returned to baseline levels in morphine-treated wounds. Similarly, both SP- and CGRP-ir in 129S6 and MOR-KO were increased significantly in PBS-treated mice but not in morphine-treated as compared to baseline before wounding. It is noteworthy, that SP- and CGRP-ir were significantly higher in the unwounded skin of MOR-, DOR- and KOR-KO as compared to 129S6 control mice, suggesting that all three ORs are involved in the regulation of neuropeptides. Therefore, even though wound healing and blood flow were not influenced by morphine in MOR-KO, neuropeptides were responsive to morphine treatment in MOR-KO. Together, these data suggest that MOR downregulation may contribute to impaired wound healing and that other ORs are critical to regulate neuropeptides to control neurogenic inflammation in the skin, which may in turn influence the healing process. Thus, morphine orchestrates wound healing by stimulating vascular function via MOR and modulating neurogenic inflammation via ORs in the skin. Since increased inflammation and vasculopathy underlie wound pathobiology in SCD, morphine may have a therapeutic effect on healing leg ulcers. Disclosures: No relevant conflicts of interest to declare.

scholarly journals A Computationally Designed Water-Soluble Variant of a G-Protein-Coupled Receptor: The Human Mu Opioid Receptor

PLoS ONE ◽  
2013 ◽  
Vol 8 (6) ◽  
pp. e66009 ◽  
Author(s):  
Jose Manuel Perez-Aguilar ◽  
Jin Xi ◽  
Felipe Matsunaga ◽  
Xu Cui ◽  
Bernard Selling ◽  
...  
Keyword(s):  
G Protein ◽  
Opioid Receptor ◽  
Mu Opioid Receptor ◽  
Water Soluble ◽  
G Protein Coupled Receptor ◽  
Mu Opioid ◽  
G Protein Coupled

scholarly journals Mu opioid receptor and orexin/hypocretin mRNA levels in the lateral hypothalamus and striatum are enhanced by morphine withdrawal

2006 ◽  
Vol 191 (1) ◽  
pp. 137-145 ◽  
Author(s):  
Yan Zhou ◽  
Jacob Bendor ◽  
Lauren Hofmann ◽  
Matthew Randesi ◽  
Ann Ho ◽  
...  
Keyword(s):  
Opioid Receptor ◽  
Lateral Hypothalamus ◽  
Brain Regions ◽  
Mu Opioid Receptor ◽  
Morphine Withdrawal ◽  
Mrna Levels ◽  
Chronic Morphine ◽  
Mu Opioid ◽  
Morphine Administration ◽  
Related Stress

In this study, we investigated the effects of acute morphine administration, chronic intermittent escalating-dose morphine administration and spontaneous withdrawal from chronic morphine on mRNA levels of mu opioid receptor (MOP-r), and the opioid peptides pro-opiomelanocortin (POMC) and preprodynorphin (ppDyn) in several key brain regions of the rat, associated with drug reward and motivated behaviors: lateral hypothalamus (lat.hyp), nucleus accumbens (NAc) core, amygdala, and caudate–putamen (CPu). There was no effect on MOP-r mRNA levels in these brain regions 30 min after either a single injection of morphine (10 mg/kg, i.p.) or chronic intermittent escalating-dose morphine (from 7.5 mg/kg per day on day 1 up to 120 mg/kg per day on day 10). Activation of the stress-responsive hypothalamic–pituitary–adrenal axis by 12 h withdrawal from chronic morphine was confirmed; both POMC mRNA levels in the anterior pituitary and plasma adrenocorticotropic hormone levels were significantly elevated. Under this withdrawal-related stress condition, there was an increase in MOP-r mRNA levels in the lat.hyp, NAc core, and CPu. Recent studies have demonstrated a novel role for the lat.hyp orexin (or hypocretin) activation in both drug-related positive rewarding, and withdrawal effects. Around 50% of lat.hyp orexin neurons express MOP-r. Therefore, we also examined the levels of lat.hyp orexin mRNA, and found them increased in morphine withdrawal, whereas there was no change in levels of the lat.hyp ppDyn mRNA, a gene coexpressed with the lat.hyp orexin. Our results show that there is an increase in MOP-r gene expression in a region-specific manner during morphine withdrawal, and support the hypothesis that increased lat.hyp orexin activity plays a role in morphine-withdrawal-related behaviors.

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