Involvement of kappa-opioid receptors in peripheral response to nerve stimulation in kappa-opioid receptor knockout mice

2002 ◽  
Vol 22 (4) ◽  
pp. 233-239 ◽  
Author(s):  
D. Mitolo-Chieppa ◽  
L. Natale ◽  
F. L. Marasciulo ◽  
G. De Salvatore ◽  
C. I. Mitolo ◽  
...  
1993 ◽  
Vol 90 (23) ◽  
pp. 11429-11432 ◽  
Author(s):  
T J Grudt ◽  
J T Williams

Decrease of calcium conductance induced by opioid agonists has been reported by others for mu-, delta-, and kappa-opioid receptors. On the other hand, only mu- and delta-opioid receptors have been reported to increase potassium conductance. Intracellular recordings were made from guinea pig substantia gelatinosa neurons in a brain slice. A subset of cells (29 of 83) were hyperpolarized by the kappa-opioid receptor agonist U69593 with an EC50 of 23 nM. The kappa-opioid receptor antagonist norbinaltorphimine (10 nM) blocked the hyperpolarization by U69593 but had no effect on the mu-opioid hyperpolarization present in these cells. Naloxone (300 nM) shifted the U69593 dose-response curve to the right, giving an estimated Kd for naloxone of 7.5 and 8.1 nM measured in two cells. The hyperpolarization caused by U69593 was mediated by a potassium conductance as determined with voltage clamp experiments. This demonstrates, depending on the cell type, that all three major opioid receptors (mu, delta, and kappa) can increase potassium conductance as well as decrease calcium conductance.


1991 ◽  
Vol 261 (6) ◽  
pp. R1527-R1532 ◽  
Author(s):  
R. Vink ◽  
P. S. Portoghese ◽  
A. I. Faden

Treatment with opioid receptor antagonists improves outcome after experimental brain trauma, although the mechanisms underlying the protective actions of these compounds remain speculative. We have proposed that endogenous opioids contribute to the pathophysiology of traumatic brain injury through actions at kappa-opioid receptors, possibly by affecting cellular bioenergetic state. In the present study, the effects of the kappa-selective opioid-receptor antagonist nor-binaltorphimine (nor-BNI) were examined after fluid percussion brain injury in rats. Metabolic changes were evaluated by 31P magnetic resonance spectroscopy; the same animals were subsequently followed over 2 wk to evaluate neurological recovery. Nor-BNI, administered intravenously as a 10 or 20 mg/kg bolus at 30 min after injury, significantly improved neurological outcome at 2 wk posttrauma compared with controls. Animals treated with nor-BNI showed significantly greater recovery of intracellular free magnesium concentrations and cytosolic phosphorylation potentials during the first 4 h after injury compared with saline-treated controls. The improvement in cytosolic phosphorylation potential was significantly correlated to neurological outcome. These data support the hypothesis that kappa-opioid receptors mediate pathophysiological changes after traumatic brain injury and that the beneficial effects of opioid-receptor antagonist may result from improvement of posttraumatic cellular bioenergetics.


1984 ◽  
Vol 64 (5) ◽  
pp. 13-15 ◽  
Author(s):  
Y. RUCKEBUSCH ◽  
TH. BARDON

Intravenous adrenaline induced reticular extracontractions and rumination within 26 sec in hay-fed, and 184 sec in cube-fed sheep. Regardless of diet, pretreatment with cerebroventricular infusion of kappa-opioid-receptor agonists enhanced this reflex. Control of rumination may involve multiple opioid-receptors, since inhibition of the reflex occurred after mu- and delta-opioid-agonists. Key words: Sheep, rumination, opioid-peptides


1993 ◽  
Vol 295 (3) ◽  
pp. 625-628 ◽  
Author(s):  
Y Chen ◽  
A Mestek ◽  
J Liu ◽  
L Yu

By screening a rat brain cDNA library using a cloned mu opioid receptor cDNA as probe, a clone was identified that is very similar to both the mu and delta opioid receptor sequences. Transient expression of this clone in COS-7 cells showed that it encodes a kappa opioid receptor, designated KOR-1, which is capable of high-affinity binding to kappa-selective ligands. Treatment of transfected cell membranes with bremazocine, a kappa-selective agonist, resulted in a 53% decrease in adenylate cyclase activity, indicating that this kappa opioid receptor displays inhibitory coupling to adenylate cyclase. Thus, one member from each of the three opioid receptor types, mu, kappa and delta, has been molecularly cloned. Analysis of sequence similarities among these opioid receptors, as well as between opioid receptors and other G-protein-coupled receptors, revealed regions of sequence conservation that may underlie the ligand-binding and functional specificities of opioid receptors.


2003 ◽  
Vol 134 (1-2) ◽  
pp. 72-81 ◽  
Author(s):  
Claire Gavériaux-Ruff ◽  
Frédéric Simonin ◽  
Dominique Filliol ◽  
Brigitte L. Kieffer

2006 ◽  
Vol 105 (3) ◽  
pp. 550-556 ◽  
Author(s):  
Shi-zhong Zhang ◽  
Ning-fu Wang ◽  
Jian Xu ◽  
Qin Gao ◽  
Guo-hua Lin ◽  
...  

Background Remote preconditioning is known to be cardioprotective, but the exact mechanism has not been fully elucidated. The objective of the current study was to investigate the role of kappa-opioid receptors in cardioprotection by remote preconditioning and reveal possible underlying mechanisms. Methods Remote preconditioning was induced in anesthetized male Sprague-Dawley rats by three cycles of 5 min of right femoral artery occlusion followed by 5 min of reperfusion. Myocardial ischemia-reperfusion was achieved by ligation of the left anterior descending coronary artery for 30 min and then reperfusion for 120 min. Infarct size was determined by 2,3,5-triphenyltetrazolium chloride staining. Levels of lactate dehydrogenase, dynorphin, and met-enkephalin in plasma were measured. The opening of the mitochondrial permeability transition pore was monitored with fluorescent calcein in isolated ventricular myocytes. Results Both remote preconditioning and U-50,488H (10 mg/kg intravenous), a kappa-opioid receptor agonist, significantly decreased the infarct size and plasma lactate dehydrogenase level induced by ischemia-reperfusion, and these effects were attenuated by nor-binaltorphimine (10 mg/kg intravenous), a kappa-opioid receptor antagonist, and atractyloside (5 mg/kg intravenous), a mitochondrial permeability transition pore activator. However, administration of naltrindole (5 mg/kg), a delta-opioid receptor antagonist, had no effect on the cardioprotection by remote preconditioning. The dynorphin plasma level was increased after remote preconditioning treatment, but the met-enkephalin level did not change. In isolated ventricular myocytes loaded with calcein, U-50,488H (300 microM) decreased the mitochondrial permeability transition pore opening induced by calcium (200 microM), and this effect was attenuated by cotreatment with nor-binaltorphimine (5 microM) or atractyloside (20 microM). Conclusion Activation of cardiac kappa-opioid receptors is involved in the cardioprotection induced by remote preconditioning, and the mitochondrial permeability transition pore may participate in the postreceptor pathway.


CNS Spectrums ◽  
2020 ◽  
Vol 25 (2) ◽  
pp. 282-283
Author(s):  
Dev Patel ◽  
Ishandeep Gandhi ◽  
Faisal Malek ◽  
Camille Olechowski ◽  
Alan R. Hirsch

Abstract:Introduction:Choreaform movements provoked by opiates is an infrequent adverse event. Buprenorphine induction of chorea has not heretofore been described. Such a case is presented.METHOD:Case Study: A 38-year-old female presented with a decade long history of alcohol, cocaine, benzodiazepine, and heroin abuse. The patient was insufflating 1.5 grams of heroin daily. On presentation, she was actively withdrawing, scoring 17 on the Clinical Opioid Withdrawal Scale. Urine toxicology screening was positive for opiates, cocaine, and cannabinoids. Buprenorphine 4 mg sublingual was initiated. Within one hour, she observed, “My legs were moving uncontrollably as if I was a marionette.” These dance-like movements were isolated to both legs and gradually resolved after discontinuation of buprenorphine: most of the movements manifested in the first 8 hours, and dissipated over the next 2 days. She did have similar movements after treatment with quetiapine during a previous hospitalization, years earlier.RESULTS:Abnormalities in physical examination: General: goiter, bilateral palmar erythema. Neurological examination: Cranial Nerve (CN) Examination: CN I: Alcohol Sniff Test: 2 (anosmia). Motor Examination: Drift testing: mild right pronator drift. Reflexes: 3+ bilateral lower extremities. Neuropsychiatric Examination: Clock Drawing Test: 3 (abnormal). Animal Fluency Test: 18 (normal). Go-No-Go Test 6/6 (normal).DISCUSSION:Buprenorphine induced chorea could be a result of partial mu-opioid agonism, or kappa and delta receptor antagonism (Burke, 2018; Cowan, 1977). Mu-opioid receptor activation causes increased dopamine turnover in the nigrostriatum, which is responsible for locomotor sensitization (Campos-Jurado, 2017). With the addition of mu-opioid receptor modulation of dopamine release, kappa-opioid receptor alters various neurotransmitters in the basal ganglia, potentiating hyperkinetic movements. Buprenorphine’s choreiformogenic action may be due to kappa-opioid receptors ability to augment neurotransmission in the striatum (Escobar, 2017; Bonnet, 1998). The combination of simultaneous activity of these three opioid receptors may cause chorea, since they act to modulate dopamine, glutamate, and GABA in the direct and indirect pathways within the basal ganglia (Abin, 1989; Cui, 2013; Allouche, 2014; Trifilieff, 2013). This patient’s history of heroin and cocaine use may have caused supersensitization of dopamine receptors (Memo, 1981), provoking hyperkinesia. Involvement of substance-induced sensitization with concurrent kappa-opioid receptor neurotransmitter augmentation in direct and indirect pathways in the basal ganglia may have primed our patient to the development of chorea after buprenorphine administration. Further investigation for the presence of extrapyramidal movements in those undergoing buprenorphine treatment is warranted.


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