Biochemical and Biophysical Research Communications
Regular ArticleTissue Distribution of Opioid Receptor Gene Expression in the Rat
Abstract
The endogenous opioid peptides have multiple physiological actions at both a central and peripheral level which are mediated by 3 main classes of opioid receptors, μ, δ and κ. The rat μ, δ and κ opioid receptors have recently been cloned and their distribution of expression in the central nervous system has been mapped. In these studies we have used the reverse transcriptase polymerase chain reaction and Southern blotting to determine the distribution of expression of the μ, δ and κ opioid receptors in the peripheral tissues of the rat. All 3 opioid receptors were found to be widely expressed in several peripheral tissues including the small intestine, large intestine, adrenal, kidney, lung, spleen, testis, ovary and uterus. In the stomach, δ and κ but not μ opioid receptor transcripts were detected. Predominantly δ transcripts were detected in the heart, with no μ and only a weak signal for the κ receptor. In the liver μ and δ but not κ transcripts were present. Opioid receptor expression was not detected in endothelium or synovium. There is therefore a broad, but tissue specific distribution of opioid receptor expression in the periphery of the rat, suggesting that the endogenous opioid peptides play an endocrine, paracrine, or autocrine role in the regulation of physiology at a peripheral as well as central level.
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Meta-analysis of pre-clinical studies on the effects of opioid receptor ligands on food intake, motivation, and choice
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Impact of timing of morphine treatment on infarct size in experimental animal model of acute myocardial ischemia and reperfusion
2022, European Journal of PharmacologyMorphine is generally used in clinical treatment for the patients who have not been effectively alleviated for chest pain after the treatment with nitrites or who contraindicate nitrite drugs. However, it was reported that the treatment with morphine in acute myocardial infarction or acute coronary artery syndromes induced increase in myocardial injury even increase of the mortality of the patients. After comparing the reported laboratory studies showing the cardioprotective effects and the clinical observations presenting the harmful consequences, we query whether the timing of the morphine treatment makes the difference in the prognosis of the ischemic/infarct myocardium. We found that intravenous injections of morphine (0.3 mg/kg) at 15 min before the acute myocardial ischemia, at 5 min and 20 min or 60 min after ligation of the coronary artery in separate groups of rats scheduled for acute myocardial ischemia, for 30 min or 90 min followed by reperfusion for 120 min, induced different results, reduction in the size of infarction, no effect and increases of the infarct sizes, respectively. The opioid μ- and kappa-receptors mediated the detrimental effect of morphine on the myocardial injury. The findings of this study suggest that administration of morphine may cause different consequences when used at different time in the pathology of acute myocardial ischemia and reperfusion. The underlying mechanisms in the pathology of acute myocardial ischemia warrant further study.
Morphine and myocardial ischaemia-reperfusion
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PnAn13, an antinociceptive synthetic peptide inspired in the Phoneutria nigriventer toxin PnTx4(6–1) (δ-Ctenitoxin-Pn1a)
2020, Toxicon: XAnimal venoms are an almost inexhaustible source for promising molecules with biological activity and the venom of Phoneutria nigriventer spider is a good example of this. Among several other toxins obtained from this venom, PnTx4(6–1), also called δ-Ctenitoxin-Pn1a, was isolated and initially described as an insect toxin that binds to the site 3 of sodium channels in cockroach nerve cord synaptosomes (Periplaneta americana) and slows down sodium current inactivation in isolated axons of this animal. This toxin did not cause any apparent toxicity to mice when intracerebroventricularly injected (30 μg). Subsequently, it was demonstrated that PnTx4(6–1) has an antinociceptive effect in three different pain models: inflammatory, induced by carrageenan; nociceptive, induced by prostaglandin E2 and neuropathic, induced by sciatic nerve constriction. Using diverse antagonists from receptors, it was shown that the cannabinoid system, via the CB1 receptor, and the opioid system, through the μ and δ receptors, are both involved in the antinociceptive effect of PnTx4(6–1). In the present work, it was synthesized a peptide, named PnAn13, based on the amino acid sequence of PnTx4(6–1) in order to try to reproduce or increase the analgesic effect of the toxin. As it was seen for the toxin, PnAn13 had antinociceptive activity, when intrathecally injected, and this effect involved the cannabinoid and opioid systems. In addition, when it was evaluated the peripheral effect of PnAn13, via intraplantar administration, this peptide was able to reverse the hyperalgesic threshold, evoked by prostaglandin E2. Therefore, using different pharmacological tools, it was shown the participation of cannabinoid and opioid systems in this effect.
Opioid Peptides and Their Receptors in Chickens: Structure, Functionality, and Tissue Distribution
2020, PeptidesOpioid peptides, derived from PENK, POMC, PDYN and PNOC precursors, together with their receptors (DOR, MOR, KOR and ORL1), constitute the opioid system and are suggested to participate in multiple physiological/pathological processes in vertebrates. However, the question whether an opioid system exists and functions in non-mammalian vertebrates including birds remains largely unknown. Here, we cloned genes encoding opioid system from the chicken brain and examined their functionality and tissue expression. As in mammals, 6 opioid peptides encoded by PENK (Met-enkephalin and Leu-enkephalin), POMC (β-endorphin), PDYN (dynorphin-A and dynorphin-B) and PNOC (nociceptin) precursors and four opioid receptors were found to be highly conserved in chickens. Using pGL3-CRE-luciferase and pGL4-SRE-luciferase reporter systems, we demonstrated that chicken opioid receptors (cDOR, cMOR, cKOR and cORL1) expressed in CHO cells, could be differentially activated by chicken opioid peptides, and resulted in the inhibition of cAMP/PKA and activation of MAPK/ERK signaling pathways. cDOR is potently activated by Met-enkephalin and Leu-enkephalin, and cKOR is potently activated by dynorphin-A, dynorphin-B and nociceptin, whereas cORL1 is specifically activated by nociceptin. Unlike cDOR, cKOR and cORL1, cMOR is moderately/weakly activated by enkephalins and other opioid peptides. These findings suggest the ligand-receptor pair in chicken opioid system is similar, but not identical to, that in mammals. Quantitative real-time PCR revealed that the opioid system is mainly expressed in chicken central nervous system including the hypothalamus. Collectively, our data will help to facilitate the better understanding of the conserved roles of opioid system across vertebrates.
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