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Opioid Receptor Activation (opioid + receptor_activation)
Selected AbstractsIn Vivo Modulation of Post-Spike Excitability in Vasopressin Cells by ,-Opioid Receptor ActivationJOURNAL OF NEUROENDOCRINOLOGY, Issue 8 2000C. H. Brown Abstract An endogenous ,-opioid agonist reduces the duration of phasic bursts in vasopressin cells. Non-synaptic post-spike depolarizing after-potentials underlie activity during bursts by increasing post-spike excitability and ,-receptor activation reduces depolarizing after-potential amplitude in vitro. To investigate the effects of ,-opioids on post-spike excitability in vivo, we analysed extracellular recordings of the spontaneous activity of identified supraoptic nucleus vasopressin cells in urethane-anaesthetized rats infused with Ringer's solution (n = 17) or the ,-agonist, U50,488H (2.5 µg/h at 0.5 µl/h; n = 23), into the supraoptic nucleus over 5 days. We plotted the mean hazard function for the interspike interval distributions as a measure of the post-spike excitability of these cells. Following each spike, the probability of another spike firing in vasopressin cells recorded from U50,488H infused nuclei was markedly reduced compared to Ringer's treated vasopressin cells. To determine whether U50,488H could reduce post-spike excitability in cells that displayed spontaneous phasic activity, we infused U50,488H (50 µg/h at 1 µl/h, i.c.v.), for 1,12 h while recording vasopressin cell activity. Nine of 10 vasopressin cells were silenced by i.c.v. U50,488H 15 ± 5 min into the infusion. Six cells exhibited spontaneous phasic activity before U50,488H infusion and recordings from three of these phasic cells were maintained until activity recovered; during U50,488H infusion, the activity of these three cells was irregular. Generation of the mean hazard function before and during U50,488H infusion revealed a reduction in post-spike excitability during U50,488H infusion. Thus, ,-receptor activation reduces post-spike excitability in vivo; this may reflect inhibition of depolarizing after-potentials and may thus underlie the reduction in burst duration of vasopressin cells caused by an endogenous ,-agonist in vivo. [source] Constitutive opioid receptor activation: a prerequisite mechanism involved in acute opioid withdrawalADDICTION BIOLOGY, Issue 2 2005E Freye The opioid receptor antagonist naltrexone, which is used in detoxification and rehabilitation programmes in opioid addicts, can precipitate opioid withdrawal symptoms even in patients who have no opioid present. We tested the hypothesis that in order to precipitate withdrawal, opioids need to convert the inactive opioid receptor site via protein kinase C into a constitutively active form on which the antagonist precipitates withdrawal. Acute abstinence symptoms were induced by the potent opioid receptor agonist sufentanil (21?,g/kg), given for 6 days, which was followed by the antagonist naltrexone (20?,g/kg i.v.) in the awake trained canine (n,=,10). Abrupt displacement of opioid binding resulted in acute withdrawal symptoms: increase in blood pressure, heart rate, increase in amplitude height of somatosensory evoked potential, reduced tolerance to colon distention and a significant increase in grading of vegetative variables (restlessness, panting, thrashing of the head, whining, yawning, gnawing, salivation and/or rhinorrhoea, mydriasis, stepping of extremities and vomiting). Following a washout period of 14 days, the same animals were given the highly specific protein kinase C inhibitor H7 (250?,g/kg) prior to the same dosages of sufentanil and naltrexone. Such pretreatment was able to either attenuate or completely abolish the acute withdrawal symptoms. The data suggest that for precipitation of withdrawal, intracellular phosphorylation is a prerequisite in order to activate the opioid ,-receptor. In such a setting, naltrexone acts like an ,inverse agonist? relative to the action of the antagonist on a non-preoccupied receptor site not being exposed previously to a potent opioid agonist. [source] Modulation of systemic and renal haemodynamics by ,-opioids in conscious lambsEXPERIMENTAL PHYSIOLOGY, Issue 5 2006Wei Qi The purpose of the present study was to determine the cardiovascular effects of the ,-opioid receptor agonist U-50488H at two stages of postnatal maturation under physiological conditions. Experiments were carried out firstly to define systemic and renal haemodynamic responses to ,-opioid receptor activation and, secondly, to determine whether these effects are altered during postnatal maturation. To investigate whether the responses to U-50488H resulted from receptor-dependent effects, responses to U-50488H were also tested in the presence of the specific ,-opioid receptor antagonist 5,-guanidinonaltrindole (GNTI). Experiments were carried out in two groups of conscious, chronically instrumented lambs aged ,1 and ,6 weeks. Mean arterial pressure, mean venous pressure and renal blood flow (RBF) were measured for 30 min before and 90 min after i.v. injection of U-50488H or vehicle. Heart rate increased in both age groups of lambs within 10 min of U-50488H administration. Mean arterial pressure decreased for 50 min following U-50488H administration at 1 week but, in contrast, increased transiently at 10 min in 6-week-old lambs, returning to control levels by 20 min. In both age groups, there was a sustained decrease in RBF following U-50488H. The aforementioned responses to U-50488H were abolished by pretreatment with GNTI. These data provide the first measurements of systemic and renal haemodynamic responses to ,-opioid receptor activation during postnatal maturation. [source] Remote pharmacological post-conditioning by intrathecal morphine: cardiac protection from spinal opioid receptor activationACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 9 2010J. LING LING Background: Intrathecal morphine pre-conditioning attenuates cardiac ischemia,reperfusion injury via activation of central opioid receptors. We hypothesized that intrathecal morphine also post-conditions the myocardium in the rat. Methods: Intrathecal morphine at 0.3 ,g/kg (LMPC), 3 ,g/kg (MMPC) or 30 ,g/kg (HMPC) was administered for 5 min before 120-min reperfusion following 30-min ischemia. Infarct size as a percentage of area at risk (IS/AAR) was determined using triphenyltetrazolium staining. MMPC was repeated following the intrathecal administration of nor BNI, NTD, CTOP, or naloxone methiodide (NM), kappa, delta, mu and non-specific opioid receptor antagonists, respectively. The role of peripheral opioid, adenosine and calcitonin gene-related peptide (CGRP) receptors was examined by the intravenous administration of NM, 8-,-sulfophenyl theophylline (8-SPT) and human CGRP fragment (CGRP8,37), respectively. Results: Morphine post-conditioning at all three doses was cardioprotective (IS/AAR of LMPC=37±4%, MMPC=35±5%, HMPC=32±4%, control=50±5%, P<0.01). The prior administration of opioid receptor antagonists intrathecally, as well as intravenous 8-SPT and CGRP8,37 receptor antagonists, abolished this effect (nor BNI+MMPC=47±7%, NTD+MMPC=49±7%, CTOP+MMPC=45±9%, NM+MMPC=47±6% 8-SPT+MPC=46±5% & CGRP8,37+MPC=53±6%, P=0.63). However, the intravenous administration of NM did not prevent the protective effect (34±4%, P<0.01). Conclusions: Intrathecal morphine administration can induce pharmacological cardiac post-conditioning as it involves opioid receptor centrally but non-opioid receptors peripherally. [source] Remifentanil post-conditioning attenuates cardiac ischemia,reperfusion injury via , or , opioid receptor activationACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 4 2010G. T. C. WONG Background: Ischemic pre- or post-conditioning of the heart has been shown to involve opioid receptors. Remifentanil, an ultra-short-acting selective , opioid receptor agonist in clinical use, pre-conditions the rat heart against ischemia,reperfusion injury. This study investigates whether remifentanil post-conditioning is also cardioprotective. Methods: Remifentanil post-conditioning (5-min infusion at 1, 5, 10 or 20 ,g/kg/min) or ischemic post-conditioning (three cycles of a 10 s reperfusion interspersed with a 10 s ischemia) was induced in an open-chest rat heart model of ischemia and reperfusion injury, in the presence or absence of nor-binaltorphimine, naltrindole or CTOP, specific ,, , and , opioid receptor antagonists, respectively. The same sequence of experiments was repeated in the isolated heart model using the maximal protective dose of remifentanil from the dose,response studies. Results: Both ischemic and remifentanil post-conditioning reduced the myocardial infarct size relative to the control group in both models. This cardioprotective effect for both post-conditioning regimes was prevented by the prior administration of nor-binaltorphimine and naltrindole but not CTOP. The sole administration of the antagonists had no effect on the size of myocardial infarction. Conclusions: These results indicate that remifentanil post-conditioning protects the heart from ischemia,reperfusion injury to a similar extent as of ischemic post-conditioning. This protection involves , and , but not , opioid receptor activation. This drug has great potential as a clinical post-conditioning modality as it can be given in large doses without prolonged opioid-related side effects. [source] Morphine and HIV-Tat increase microglial-free radical production and oxidative stress: possible role in cytokine regulationJOURNAL OF NEUROCHEMISTRY, Issue 1 2009Jadwiga Turchan-Cholewo Abstract Opiate abuse alters the progression of human immunodeficiency virus and may increase the risk of neuroAIDS. As neuroAIDS is associated with altered microglial reactivity, the combined effects of human immunodeficiency virus-Tat and morphine were determined in cultured microglia. Specifically, experiments determined the effects of Tat and morphine on microglial-free radical production and oxidative stress, and on cytokine release. Data show that combined Tat and morphine cause early and synergistic increases in reactive oxygen species, with concomitant increases in protein oxidation. Furthermore, combined Tat and morphine, but not Tat or morphine alone, cause reversible decreases in proteasome activity. The effects of morphine on free radical production and oxidative stress are prevented by pre-treatment with naloxone, illustrating the important role of opioid receptor activation in these phenomena. While Tat is well known to induce cytokine release from cultured microglia, morphine decreases Tat-induced release of the cytokines tumor necrosis factor-, and interleukin-6, as well as the chemokine monocyte chemoattractant protein-1 (MCP-1). Finally, experiments using the reversible proteasome inhibitor MG115 show that temporary, non-cytotoxic decreases in proteasome activity increase protein oxidation and decrease tumor necrosis factor-,, interleukin-6, and MCP-1 release from microglia. Taken together, these data suggest that oxidative stress and proteasome inhibition may be involved in the immunomodulatory properties of opioid receptor activation in microglia. [source] Cellular Actions Of Opioids And Other Analgesics: Implications For Synergism In Pain ReliefCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 7 2000MacDonald J Christie SUMMARY 1. ,-Opioid receptor agonists mediate their central analgesic effects by actions on neurons within brain regions such as the mid-brain periaqueductal grey (PAG). Within the PAG, ,-opioid receptor-mediated analgesia results from inhibition of GABAergic influences on output projection neurons. We have established that ,-opioid receptor activation in the PAG causes a presynaptic inhibition of GABA release that is mediated by activation of a voltage-dependent K+ channel via 12-lipoxygenase (LOX) metabolites of arachidonic acid. 2. At a cellular level, ,-opioid agonists have also been shown to open inwardly rectifying K+ channels, close voltage-gated Ca2+ channels and presynaptically inhibit glutamatergic synaptic transmission in the PAG. 3. The ,-opioid receptor-mediated presynaptic inhibition of GABAergic transmission was abolished by phospholipase A2 inhibitors and non-specific LOX and specific 12-LOX inhibitors. Cyclo-oxygenase (COX) and specific 5-LOX inhibitors did not reduce the inhibitory effects of ,-opioid agonists. 4. The opioid actions on GABAergic transmission were mimicked by arachidonic acid and 12-LOX metabolites, but not 5-LOX metabolites. The efficacy of ,-opioids was enhanced synergistically by treatment of PAG neurons with inhibitors of the other major enzymes responsible for arachidonic acid metabolism, COX and 5-LOX. 5. These results explain a previously described analgesic action of COX inhibitors in the central nervous system that was both independent of prostanoid release and inhibited by opioid receptor antagonists and they also explain the synergistic interaction of opioids with COX inhibitors. These findings also suggest new avenues for the development of centrally active analgesic agents involving combinations of lowered doses of opioids and specific 5-LOX inhibitors. [source] | |||||||||||||