scholarly journals Activation of peripheral opioid κ1 receptor prevents cardiac reperfusion injury

2021 ◽  
pp. 523-531
Author(s):  
Sergey V. Popov ◽  
Alexander V. Mukhomedzyanov ◽  
Sergey Y. Tsibulnikov ◽  
Igor Khaliulin ◽  
Peter R. Oeltgen ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Opioid Receptor ◽  
Receptor Agonist ◽  
Cardiac Injury ◽  
Coronary Artery Occlusion ◽  
Artery Occlusion ◽  
Receptor Antagonists ◽  
Area At Risk ◽  
Opioid Receptor Antagonists ◽  
Κ Receptor

The role of opioid κ1 and κ2 receptors in reperfusion cardiac injury was studied. Male Wistar rats were subjected to a 45-min coronary artery occlusion followed by a 120-min reperfusion. Opioid κ receptor agonists were administered intravenously 5 min before the onset of reperfusion, while opioid receptor antagonists were given 10 min before reperfusion. The average value of the infarct size/area at risk (IS/AAR) ratio was 43 – 48 % in untreated rats. Administration of the opioid κ1 receptor agonist (-)-U-50,488 (1 mg/kg) limited the IS/AAR ratio by 42 %. Administration of the opioid κ receptor agonist ICI 199,441 (0.1 mg/kg) limited the IS/AAR ratio by 41 %. The non-selective opioid κ receptor agonist (+)-U-50,488 (1 mg/kg) with low affinity for opioid κ receptor, the peripherally acting opioid κ receptor agonist ICI 204,448 (4 mg/kg) and the selective opioid κ2 receptor agonist GR89696 (0.1 mg/kg) had no effect on the IS/AAR ratio. Pretreatment with naltrexone, the peripherally acting opioid receptor antagonist naloxone methiodide, or the selective opioid κ receptor antagonist nor-binaltorphimine completely abolished the infarct-reducing effect of (-)-U-50,488 and ICI 199,441. Pretreatment with the selective opioid δ receptor antagonist TIPP[ψ] and the selective opioid µ receptor antagonist CTAP did not alter the infarct reducing effect of (-)-U-50,488 and ICI 199,441. Our study is the first to demonstrate the following: (a) the activation of opioid κ2 receptor has no effect on cardiac tolerance to reperfusion; (b) peripheral opioid κ1 receptor stimulation prevents reperfusion cardiac injury; (c) ICI 199,441 administration resulted in an infarct-reducing effect at reperfusion; (e) bradycardia induced by opioid κ receptor antagonists is not dependent on the occupancy of opioid κ receptor.

scholarly journals TAN-67, a δ1-opioid receptor agonist, reduces infarct size via activation of Gi/oproteins and KATPchannels

1998 ◽  
Vol 274 (3) ◽  
pp. H909-H914 ◽  
Author(s):  
Jo El J. Schultz ◽  
Anna K. Hsu ◽  
Hiroshi Nagase ◽  
Garrett J. Gross
Keyword(s):  
Infarct Size ◽  
Opioid Receptor ◽  
Opioid Receptors ◽  
Coronary Artery Occlusion ◽  
Receptor Activation ◽  
Artery Occlusion ◽  
Cardioprotective Effect ◽  
Area At Risk ◽  
Opioid Receptor Agonist ◽  
Δ Opioid Receptor

We have previously shown that delta (δ)-opioid receptors, most notably δ1, are involved in the cardioprotective effect of ischemic preconditioning (PC) in rats; however, the mechanism by which δ-opioid receptor-induced cardioprotection is mediated remains unknown. Therefore, we hypothesized that several of the known mediators of ischemic PC such as the ATP-sensitive potassium (KATP) channel and Gi/oproteins are involved in the cardioprotective effect produced by δ1-opioid receptor activation. To address these possibilities, anesthetized, open-chest Wistar rats were randomly assigned to five groups. Control animals were subjected to 30 min of coronary artery occlusion and 2 h of reperfusion. To demonstrate that stimulating δ1-opioid receptors produces cardioprotection, TAN-67, a new selective δ1-agonist, was infused for 15 min before the long occlusion and reperfusion periods. In addition, one group received 7-benzylidenenaltrexone (BNTX), a selective δ1-antagonist, before TAN-67. To study the involvement of KATPchannels or Gi/oproteins in δ1-opioid receptor-induced cardioprotection, glibenclamide (Glib), a KATPchannel antagonist, or pertussis toxin (PTX), an inhibitor of Gi/oproteins, was administered before TAN-67. Infarct size (IS) as a percentage of the area at risk (IS/AAR) was determined by tetrazolium stain. TAN-67 significantly reduced IS/AAR as compared with control (56 ± 2 to 27 ± 5%, n = 5, P < 0.05). The cardioprotective effect of TAN-67 was completely abolished by BNTX, Glib, and PTX (51 ± 3, 53 ± 5, and 61 ± 4%, n = 6 for each group, respectively). These results are the first to suggest that stimulating the δ1-opioid receptor elicits a cardioprotective effect that is mediated via Gi/oproteins and KATPchannels in the intact rat heart.

Central opioid receptors mediate glucoprivic inhibition of pituitary LH secretion

1997 ◽  
Vol 272 (4) ◽  
pp. E517-E522 ◽  
Author(s):  
K. P. Briski
Keyword(s):  
Receptor Antagonist ◽  
Opioid Receptor ◽  
Hormone Secretion ◽  
Male Rats ◽  
Pituitary Hormone ◽  
Intracerebroventricular Administration ◽  
Receptor Antagonists ◽  
Opioid Receptor Antagonist ◽  
Opioid Receptor Antagonists

The present studies investigated the significance of glucoprivic metabolic signals, particularly those of central origin, to the regulation of pituitary luteinizing hormone (LH). Groups of gonadectomized (GDX) adult male rats were treated with 2-deoxy-D-glucose (2-DG), an inhibitor of glycolysis, by either intravenous (50, 100, or 200 mg/kg) or intracerebroventricular (5, 20, or 100 microg/rat) administration. Systemic drug treatment caused a significant decrease in mean plasma LH levels compared with saline-treated controls. Intracerebroventricular administration of 2-DG was also efficacious in suppressing circulating LH; animals treated with either of the two highest doses of the drug exhibited a significant reduction in plasma LH. In vitro studies examined direct effects of 2-DG on pituitary gonadotrope secretory activity. Exposure of anterior pituitary tissue to 2-DG during short-term perfusion had no significant impact upon either basal or gonadotropin-releasing hormone-stimulated LH release. Finally, groups of GDX rats were pretreated by intracerebroventricular administration of either the nonselective opioid receptor antagonist, naltrexone, or the selective mu-opioid receptor antagonist, beta-funaltrexamine (beta-FNA), before intravenous injection of 2-DG. Both receptor antagonists were observed to attenuate the suppressive effects of 2-DG on circulating LH in these animals. In summary, treatment of GDX rats with the glucose antimetabolite, 2-DG, decreased plasma LH, suggesting that metabolic signaling of cellular glucose oxidation is of physiological importance to the regulation of pituitary hormone secretion. Findings that plasma LH was diminished in animals treated intracerebroventricularly with 2-DG implicate central glucoprivic receptors in neuroendocrine mechanisms governing the reproductive endocrine axis. Attenuation of 2-DG-induced decreases in circulating LH by opioid receptor antagonists suggests that these receptors, particularly the mu-subtype, mediate central effects of glucoprivation on circulating LH.

Functional localization of specific receptors mediating gastrointestinal motor correlates of vomiting

1989 ◽  
Vol 256 (1) ◽  
pp. G92-G99 ◽  
Author(s):  
I. M. Lang ◽  
J. Marvig
Keyword(s):  
Small Intestine ◽  
Opioid Receptor ◽  
Opioid Receptors ◽  
Receptor Agonist ◽  
Sch 23390 ◽  
Receptor Antagonists ◽  
Motor Responses ◽  
Opioid Receptor Agonist ◽  
Opioid Receptor Antagonists ◽  
Gastrointestinal Motor

The gastrointestinal motor correlates of vomiting consist of two contractile events, 1) a giant retrogradely propagated contraction of the upper small intestine, the retrograde giant contraction (RGC) and 2) a series of post-RGC phasic contractions that occur primarily in the lower small intestine. The effects of cholinergic, dopaminergic, serotonergic, and opioid receptor antagonists and an opioid receptor agonist on vomiting and its gastrointestinal motor correlates initiated by apomorphine (APO), CuSO4, or cholecystokinin octapeptide (CCK-8) were determined in awake dogs. Atropine blocked the retrograde giant contraction only, and hexamethonium blocked all jejunoileal motor responses activated by APO, CuSO4, or CCK-8. Domperidone blocked all effects of APO only, whereas haloperidol, methysergide, 1-(1-naphthyl) piperazine, and fentanyl blocked or inhibited responses to both APO and CuSO4. None of the dopaminergic, serotonergic, or opioid receptor antagonists or the opioid receptor agonist affected the gastrointestinal motor responses to CCK-8. Cinanserin or Sch 23390 had no effect on any of the responses activated by APO, CuSO4, or CCK-8. These results suggested that D2 dopaminergic and 5-HT2 serotonergic receptors of the emetic central pattern generator mediate vomiting and its gastrointestinal motor correlates, whereas opioid receptors may mediate tonic inhibition of these responses. In addition, peripheral muscarinic or nicotinic cholinergic receptors but not peripheral 5-HT2, dopaminergic, or opioid receptors mediate the gastrointestinal motor correlates of vomiting.

Essential activation of PKC-δ in opioid-initiated cardioprotection

2001 ◽  
Vol 280 (3) ◽  
pp. H1346-H1353 ◽  
Author(s):  
Ryan M. Fryer ◽  
Yigang Wang ◽  
Anna K. Hsu ◽  
Garrett J. Gross
Keyword(s):  
Opioid Receptor ◽  
Coronary Artery Occlusion ◽  
Artery Occlusion ◽  
Immunofluorescent Staining ◽  
Opioid Antagonist ◽  
Area At Risk ◽  
Receptor Stimulation ◽  
Gf 109203X ◽  
Δ Opioid Receptor

Stimulation of the δ1-opioid receptor confers cardioprotection to the ischemic myocardium. We examined the role of protein kinase C (PKC) after δ-opioid receptor stimulation with TAN-67 ord-Ala2-d-Leu5-enkephalin (DADLE) in a rat model of myocardial infarction induced by a 30-min coronary artery occlusion and 2-h reperfusion. Infarct size (IS) was determined by tetrazolium staining and expressed as a percentage of the area at risk (IS/AAR). Control animals, subjected to ischemia and reperfusion, had an IS/AAR of 59.9 ± 1.8. DADLE and TAN-67 administered before ischemia significantly reduced IS/AAR (36.9 ± 3.9 and 36.7 ± 4.7, respectively). The δ1-selective opioid antagonist 7-benzylidenenaltrexone (BNTX) abolished TAN-67-induced cardioprotection (54.4 ± 1.3). Treatment with the PKC antagonist chelerythrine completely abolished DADLE- (61.8 ± 3.2) and TAN-67-induced cardioprotection (55.4 ± 4.0). Similarly, the PKC antagonist GF 109203X completely abolished TAN-67-induced cardioprotection (54.6 ± 6.6). Immunofluorescent staining with antibodies directed against specific PKC isoforms was performed in myocardial biopsies obtained after 15 min of treatment with saline, chelerythrine, BNTX, or TAN-67 and chelerythrine or BNTX in the presence of TAN-67. TAN-67 induced the translocation of PKC-α to the sarcolemma, PKC-β1 to the nucleus, PKC-δ to the mitochondria, and PKC-ε to the intercalated disk and mitochondria. PKC translocation was abolished by chelerythrine and BNTX in TAN-67-treated rats. To more closely examine the role of these isoforms in cardioprotection, we utilized the PKC-δ selective antagonist rottlerin. Rottlerin abolished opioid-induced cardioprotection (48.9 ± 4.8) and PKC-δ translocation without affecting the translocation of PKC-α, -β1, or -ε. These results suggest that PKC-δ is a key second messenger in the cardioprotective effects of δ1-opioid receptor stimulation in rats.

Behavioral Effects of Opioid Receptor Antagonists in Psychopathologic States

1983 ◽  
Vol 6 (3) ◽  
pp. 403-414 ◽  
Author(s):  
David S. Janowsky ◽  
Lewis L. Judd ◽  
Leighton Y. Huey ◽  
Samuel Craig Risch ◽  
David S. Segal
Keyword(s):  
Opioid Receptor ◽  
Behavioral Effects ◽  
Receptor Antagonists ◽  
Opioid Receptor Antagonists

scholarly journals Are opioid receptor antagonists adequate for “Opioid” overdose in a changing reality?

2021 ◽  
Author(s):  
John F. Peppin ◽  
Joseph V. Pergolizzi ◽  
Albert Dahan ◽  
Robert B. Raffa
Keyword(s):  
Opioid Receptor ◽  
Opioid Overdose ◽  
Receptor Antagonists ◽  
Opioid Receptor Antagonists
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