We investigated the mechanisms underlying MOR desensitization, in adult mammalian neurons, caused by morphine (a partial agonist in this system) and DAMGO (a high-efficacy agonist). (bath.ac.uk)
CONCLUSIONS AND IMPLICATIONS: In mature mammalian neurons, different MOR agonists can induce MOR desensitization by different mechanisms, morphine by a PKCalpha-mediated, heterologous mechanism and DAMGO by a GRK-mediated, homologous mechanism. (bath.ac.uk)
The μ-opioid receptor (MOP-R) agonist [D-Ala 2 ,N-Me-Phe 4 ,Gly 5 -ol]-enkephalin (DAMGO) also produced dose-dependent flexor response in same dose ranges. (illinois.edu)
DAMGO ([D-Ala2, N-MePhe4, Gly-ol]-enkephalin) is a synthetic opioid peptide with high μ-opioid receptor specificity. (wikipedia.org)
Intrathecal (i.t.) administration of peptidic MOR agonist [D-Ala 2 , N-Me-Phe 4 ,Gly 5 -ol]-enkephalin (DAMGO, 0.00032-0.01 mg) evoked scratching, but i.v, DAMGO (0.01-1 mg/kg) did not increase scratching. (ewha.ac.kr)
Opioid12
It was synthesized as a biologically stable analog of δ-opioid receptor-preferring endogenous opioids, leu- and met-enkephalin. (wikipedia.org)
Intravenous (i.v.) administration of μ opioid receptor (MOR) agonists (fentanyl, alfentanil, remifentanil, and morphine) evoked scratching in a dose- and time-dependent manner. (ewha.ac.kr)
Antagonist studies revealed that i.v. administration of an opioid receptor antagonist (naltrexone, 0.0032-0.1 mg/kg) dose dependently attenuated scratching induced by i.v. fentanyl (0.018 mg/kg) or morphine (1 mg/kg). (ewha.ac.kr)
However, a peripherally selective opioid antagonist (quaternary naltrexone, 0.0032-0.32 mg/kg) did not block i.v. fentanyl- or morphine-induced scratching. (ewha.ac.kr)
Pretreatment with a selective MOR antagonist (clocinnamox, 0.1 mg/kg), but not κ or δ opioid antagonists (nor-binaltorphimine or naltrindole), blocked i.t. morphine-induced scratching. (ewha.ac.kr)
opioid receptor in the brain determined by the [tylosil-3,5-(3)H(N)]-[d-Ala(2),N-MePhe(4),Gly-ol(5)]enkephalin binding assay was not significantly changed by a deletion of the dopamine D(3) receptor gene. (opioids.wiki)
In slices from morphine-dependent rats maintained in morphine (5 μ m ) in vitro , action potential frequencies of opioid-sensitive neurons did not differ from untreated control neurons but were greater than in control neurons maintained in morphine in vitro , indicating development of tolerance. (jneurosci.org)
Naloxone (100 n m or 1 μ m ) depolarized 25 of 51 neurons from morphine-dependent rats maintained in morphine in vitro , 19 of which previously had been classified as opioid-sensitive. (jneurosci.org)
Action potential frequencies in the presence of naloxone were greater than in control neurons in the absence of opioids, as well as in control neurons in the presence of both morphine and naloxone, demonstrating opioid withdrawal. (jneurosci.org)
In slices from control animals, opioid-induced hyperpolarizations and naloxone-induced depolarizations (in the presence of morphine) reversed polarity near expected E K (−111 ± 3 mV and −113 ± 3 mV, respectively). (jneurosci.org)
Naloxone2
Morphine-induced flexor responses were markedly inhibited by naloxone and D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr amide (CTOP) both MOP-R antagonists and by intrathecal injection of antisense oligodeoxynucleotide (AS-ODN) for MOP-R which is expected to reduce the receptor expression in sensory nerve endings. (illinois.edu)
Naloxone-induced depolarizations were not inhibited by tetrodotoxin (1 μ m ), bicuculline (30 μ m ), 6-cyano-7-nitroquinoxaline-2,3-dione (10 μ m ), or prazosin (300 n m ), suggesting no involvement of major synaptic neurotransmitters. (jneurosci.org)
Receptors1
furthermore, oxytocin-induced synaptic plasticity requires activation of nucleus accumbens 5-ht1b receptors, the blockade of which prevents social reward. (cognitive-liberty.online)
Amino1
The central theme of this methodology is the formation of alpha -aminoalkyl radicals from existing amino acid and alpha -amino alcohol derivatives by 1,5-hydrogen atom transfer and the subsequent trapping of these radicals with appropriate radicalphiles, thus generating quaternary centres with high efficiency and excellent stereocontrol. (exeter.ac.uk)
Locus coeruleus1
Further, the PKC component of morphine-induced desensitization was absent in locus coeruleusneurons from PKCalpha knockout mice. (bath.ac.uk)
Intracellular1
However, thapsigargin, a depletor of intracellular Ca 2+ concentration and diphenhydramine, a histamine (His) H1 receptor antagonist, were unable to block the morphine-induced flexor responses. (illinois.edu)
Dose2
In this report, we demonstrated that peripheral application of very low dose (amol ranges) of morphine induced flexor response through a substance P (SP) release at the nociceptor endings in mice. (illinois.edu)
The intraplantar (i.pl.) application of morphine produced flexor response in a dose-dependent manner from 0.1 to 1000amol. (illinois.edu)
Activation2
These results suggest that extremely low doses of morphine can stimulate sensory nerve endings through activation of peripheral MOP-R and its downstream mechanisms include activation of PLC through a SP release from polymodal C fibers. (illinois.edu)
Furthermore, we found that no significant differences in G-protein activation by morphine in the limbic forebrain and lower midbrain were noted between the two genotypes. (opioids.wiki)
RESULTS1
KEY RESULTS: Morphine-induced desensitization was attenuated by using RACK inhibitors that inhibit PKCalpha, but not by other isoform-specific inhibitors. (bath.ac.uk)
Effect3
To ascertain the morphine-induced rewarding effect in both genotypes, the conditioned place preference paradigm was performed. (opioids.wiki)
Deletion of the dopamine D(3) receptor gene resulted in a remarkable enhancement of the morphine-induced rewarding effect. (opioids.wiki)
Under these conditions, a loss of the dopamine D(3) receptor gene had no effect on the basal levels of dopamine and the increased dopamine turnover by morphine in the limbic forebrain. (opioids.wiki)
Receptors3
1. Effects of NMDA receptor antagonists on inhibition of morphine tolerance in rats: binding at mu-opioid receptors. (nih.gov)
14. Involvement of glutamatergic receptors in the nucleus cuneiformis in modulating morphine-induced antinociception in rats. (nih.gov)
Nerve ligation1
17. The loss of antinociceptive efficacy of spinal morphine in rats with nerve ligation injury is prevented by reducing spinal afferent drive. (nih.gov)
Endogenous2
It was synthesized as a biologically stable analog of δ-opioid receptor-preferring endogenous opioids, leu- and met-enkephalin. (wikipedia.org)
One of the endogenous pentapeptides with morphine-like activity. (nih.gov)
OPIOID RECEPTOR1
The mouse mu opioid receptor (OPRM1) gene undergoes extensive alternative splicing at both the 3'- and 5'-ends of the gene. (biomedcentral.com)
Antinociceptive5
In this model, intrathecal morphine shows no antiallodynic activity, as well as decreased antinociceptive potency and efficacy. (nih.gov)
This study was designed to explore the antinociceptive activity of intrathecal clonidine alone or in combination with intrathecal morphine (1:3 fixed ratio) in nerve-injured rats. (nih.gov)
The aims, with this study, were to use nerve-injured animals to determine: (1) whether the antinociceptive potency and efficacy of intrathecal clonidine was altered, and (2) whether the combination of intrathecal morphine and clonidine would act synergistically to produce antinociception. (nih.gov)
2. Competitive and non-competitive NMDA antagonists block the development of antinociceptive tolerance to morphine, but not to selective mu or delta opioid agonists in mice. (nih.gov)
18. Effect of MK-801 on the antinociceptive effect of [D-Ala(2),N-MePhe(4), Gly-ol(5)]enkephalin in diabetic mice. (nih.gov)
Opioids1
Studies in an exon 11 knockout mouse suggest the functional importance of these exon 11-associated variants in mediating the analgesic actions of a subset of mu opioids, including morphine-6β-glucuronide (M6G) and heroin, but not others such as morphine and methadone. (biomedcentral.com)
Intrathecal1
15. Increasing of intrathecal CSF excitatory amino acids concentration following morphine challenge in morphine-tolerant rats. (nih.gov)
Antinociception1
9. Dextromethorphan potentiates morphine antinociception at the spinal level in rats. (nih.gov)
Mice1
In both mice and humans 5' splicing generates a number of exon 11-containing variants. (biomedcentral.com)
Tolerance2
3. Morphine tolerance increases [3H]MK-801 binding affinity and constitutive neuronal nitric oxide synthase expression in rat spinal cord. (nih.gov)
6. Effects of NMDA receptor antagonists on morphine tolerance: a c-Fos study in the lumbar spinal cord of the rat. (nih.gov)
Clonidine1
Morphine and clonidine were given intrathecally through implanted catheters alone or in a 1:3 fixed ratio. (nih.gov)
Chronic1
Two countries at the epicenter of the opioid crisis, Canada and the United States, [ 1-4 ] recently released clinical practice guidelines for opioid prescribing for chronic noncancer pain (CNCP). (medscape.com)
Nevertheless, approximately 5%-20% of patients with EPP develop liver manifestations. (bvsalud.org)
Mouse2
Pharmacologically, disrupting exon 1 in this mouse completely abolished morphineanalgesia, but not that of either M6G or heroin, consistent with the possibility that alternatively spliced transcripts lacking exon 1 might be responsible for the residual M6G and heroin actions. (biomedcentral.com)
8. Dynorphinergic mechanism mediating endomorphin-2-induced antianalgesia in the mouse spinal cord. (nih.gov)