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  • opioids
  • 2-4 Although the occurrence of severe respiratory depression and related deaths in the treatment of acute and perioperative pain seems constant over the years (with an incidence of at least 0.5%), 1 , 5 over the last decade there has been a dramatic surge in fatalities from prescription opioids in chronic pain patients due to a dramatic increase in opioid consumption. (asahq.org)
  • 1995). Some opioids also induce opening of calcium-activated K+ channels (Stretton et al. (damasgate.com)
  • receptor
  • This was blocked by locally applied μ-receptor-selective ( d -Phe-Cys-Tyr- d -Trp-Orn-Thr-Pen-Thr-NH 2 ) but not κ-receptor-selective (nor-binaltorphimine) antagonists. (jneurosci.org)
  • δ-Receptor antagonists (naltrindole and N , N -diallyl-Tyr-Aib-Aib-Phe-Leu) did not influence EM-1-induced but dose-dependently decreased EM-2-induced antinociception. (jneurosci.org)
  • Moreover, naloxone, naltrexone, and related antagonists were compared for binding potency and effect on basal and agonist-stimulated receptor signaling, measuring guanosine 5′- O -(3-[ 35 S]thio)triphosphate binding. (aspetjournals.org)
  • yet, we have shown that release of calmodulin from the receptor by agonist stimulation uncovered the innate basal activity of MOR in the dependent state (Wang et al. (aspetjournals.org)
  • For opioid receptors, histidine, asparagine, and tyrosine residues within TM 3, 6, and 7 are critical for receptor activation (Mansour et al. (damasgate.com)
  • with the entire δ-receptor revealed 30 point mutations leading to a constitutive activity of the receptor (Decaillot et al. (damasgate.com)
  • After opioid ago- nists bind to the receptor, dissociation of the trimeric G protein complex into Gα- and Gβγ-subunits can subsequently lead to the inhibition of cyclic 3 5 adenylyl cyclase (cAMP) and/or to direct interaction with K+, Ca2+, and other ion channels in the membrane (Fig. 2a). (damasgate.com)
  • affinity
  • In vitro measures of opioid binding affinity ( K i ) and functional activity [EC 50 for agonist stimulated guanosine 5′- O -(3-[ 35 S]thio)triphosphate binding] and relevant clinical parameters were obtained to construct in vitro-to-preclinical and preclinical-to-clinical correlations. (aspetjournals.org)
  • Affinity and potency were determined using radioligand displacement and stimulation of guanosine 5′- O -(3-[ 35 S]thio)triphosphate binding in C6 (μ, δ) and Chinese hamster ovary (κ) cell membranes. (aspetjournals.org)
  • Both endomorphins competed 3 H-[ d -Ala 2 ,MePhe 4 ,Gly(ol) 5 ] enkephalin binding to MOR-1 receptors expressed in CHO cells with high affinity. (aspetjournals.org)
  • 125 I-Endomorphin-1 and 125 I-endomorphin-2 also labeled MOR-1 receptors expressed in CHO cells with high affinity. (aspetjournals.org)
  • adenylyl cyclase
  • Using guanosine 5′- O -(3-[ 35 S]thio)triphosphate ([ 35 S]GTPγS) binding and adenylyl cyclase activity assay in brain homogenates, we demonstrated that morphine pretreatment of mice enhanced basal MOR signaling in mouse brain homogenates and, moreover, caused persistent changes in the effects of naloxone and naltrexone, antagonists that elicit severe withdrawal in dependent subjects. (aspetjournals.org)
  • peripheral
  • Here we examine peripheral antinociception elicited by exogenously applied EM-1 and EM-2 and the contribution of EM-containing leukocytes to stress- and corticotropin-releasing factor (CRF)-induced antinociception. (jneurosci.org)
  • Exogenous EM-2 in addition to μ-receptors also activates peripheral δ-receptors, which does not involve actions via other opioid peptides. (jneurosci.org)
  • A prominent example is the inhibition of (pronociceptive) substance P release from primary afferent sensory neurons in the spinal cord and from their peripheral terminals (Kondo et al. (damasgate.com)
  • [4,5] Their presence in the periphery led to the hypothesis that these peripheral receptors may modulate afferent nociceptive transmission. (asahq.org)
  • amino
  • This released glutamate activates ionotropic glutamate receptors such as α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid and N -methyl-d-aspartate (NMDA) receptors in the postsynaptic membrane of the DH neurons, causing membrane depolarization and the firing of action potentials. (asahq.org)
  • desensitization
  • 4-6 Prolonged MOR activation results in desensitization of the receptors through G-protein uncoupling and subsequent neuronal excitation. (asahq.org)
  • B, β-CNA (500 nM, 2 min) was applied immediately after ME (30 μM, 10 min) induced desensitization, and recovery was again measured with ME test pulses at 5 and 45 min. (aspetjournals.org)
  • Wang
  • Wang et al. (aspetjournals.org)
  • Our laboratory has demonstrated the presence of basal MOR signaling activity in various tissues in cell culture (Wang et al. (aspetjournals.org)
  • First, morphine paradoxically enhances basal MOR signaling even though maximal agonist stimulation is blunted (Wang et al. (aspetjournals.org)
  • Naloxone and naltrexone produce little effect per se in untreated cells, acting as neutral antagonists, whereas in morphine-pretreated cells, they exhibit inverse agonist effects that suppress basal MOR activity (Wang et al. (aspetjournals.org)
  • analgesia
  • 1,2 To minimize such undesirable effects, the clinical concept of balanced or multimodal analgesia proposes to use a combination of analgesics to provide better pain relief and to minimize the side effects of each drug. (asahq.org)
  • autonomic
  • Thus inflammation of the knee joint will increase spontaneous afferent activity and produce the appearance of an exaggerated discharge with joint flexion and extension [2] and signs of a pain-associated autonomic reaction. (asahq.org)
  • membrane
  • 2 The activation of MORs result in reduction of 3′-5′-cyclic adenosine monophosphate, membrane hyperpolarization, and subsequent neuronal depression. (asahq.org)
  • proteins
  • In NG108-15 cells, muscarinic receptors and δ-opioid receptors (DOR) did not share G proteins with α 2 -adrenergic receptors (α 2 AR), as measured by agonist binding ( Graeser and Neubig, 1993 ). (aspetjournals.org)
  • tissues
  • Pain, an unpleasant experience caused by intense or damaging stimuli, is primarily protective in nature and can act as a sensorial modality to indicate the presence of tissues injury [ 1 , 2 ]. (hindawi.com)
  • rats
  • To induce inflammation, each animal (male Sprague-Dawley rats weighing 300 to 340g) was anesthetized in a Plexiglas acrylic plastic induction chamber with 2% halothane in oxygen-enriched room air. (asahq.org)