Assessment of nociceptin/orphanin FQ and μ-opioid receptor mRNA in the human right atrium

McDonald, John; Leonard, Anton; Serrano-Gomez, A; Young, S M; Swanevelder, Justiaan; Thompson, Jonathan P.; Lambert, David G.

doi:10.1093/bja/aeq089

Cited by 17 publications

(9 citation statements)

References 31 publications

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“…Most of studies failed to detect this OR subtype in the heart (Ventura et al, 1989;Zimlichman et al, 1996;Weil et al, 2006;Bolte et al, 2009;Karlsson et al, 2012). However, Head et al (2005) found the μ-OR on the sarcolemma of cardiac myocytes and its transcript was detected in the human atrium (McDonald et al, 2010). Further investigation is needed to resolve this issue.…”

Section: Discussionmentioning

confidence: 98%

Role of endogenous opioid peptides in the infarct size-limiting effect of adaptation to chronic continuous hypoxia

Maslov¹,

Нарыжная²,

Tsibulnikov³

et al. 2013

Life Sciences

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Section: Discussionmentioning

confidence: 98%

Role of endogenous opioid peptides in the infarct size-limiting effect of adaptation to chronic continuous hypoxia

Maslov¹,

Нарыжная²,

Tsibulnikov³

et al. 2013

Life Sciences

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“…5). NOP receptors are known to be present in human heart (20) and spleen, an organ rich in immune cells (21). Functional studies in exocrine pancreas of guinea pig indicated the presence of NOP receptors in pancreatic lobules (22).…”

Section: Discussionmentioning

confidence: 99%

Brain and Whole-Body Imaging of Nociceptin/Orphanin FQ Peptide Receptor in Humans Using the PET Ligand ¹¹C-NOP-1A

Lohith

Zoghbi²,

Morse³

et al. 2012

J Nucl Med

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Nociceptin/orphanin FQ peptide (NOP) receptor is a new class of opioid receptor that may play a pathophysiologic role in anxiety and drug abuse and is a potential therapeutic target in these disorders. We previously developed a high-affinity PET ligand, 11C-NOP-1A, which yielded promising results in monkey brain. Here, we assessed the ability of 11C-NOP-1A to quantify NOP receptors in human brain and estimated its radiation safety profile. Methods After intravenous injection of 11C-NOP-1A, 7 healthy subjects underwent brain PET for 2 h and serial sampling of radial arterial blood to measure parent radioligand concentrations. Distribution volume (VT; a measure of receptor density) was determined by compartmental (1- and 2-tissue) and noncompartmental (Logan analysis and Ichise’s bilinear analysis [MA1]) methods. A separate group of 9 healthy subjects underwent whole-body PET to estimate whole-body radiation exposure (effective dose). Results After 11C-NOP-1A injection, the peak concentration of radioactivity in brain was high (~5–7 standardized uptake values), occurred early (~10 min), and then washed out quickly. The unconstrained 2-tissue-compartment model gave excellent VT identifiability (~1.1% SE) and fitted the data better than a 1-tissue-compartment model. Regional VT values (mL·cm−3) ranged from 10.1 in temporal cortex to 5.6 in cerebellum. VT was well identified in the initial 70 min of imaging and remained stable for the remaining 50 min, suggesting that brain radioactivity was most likely parent radioligand, as supported by the fact that all plasma radiometabolites of 11C-NOP-1A were less lipophilic than the parent radioligand. Voxel-based MA1 VT values correlated well with results from the 2-tissue-compartment model, showing that parametric methods can be used to compare populations. Whole-body scans showed radioactivity in brain and in peripheral organs expressing NOP receptors, such as heart, pancreas, and spleen. 11C-NOP-1A was significantly metabolized and excreted via the hepatobiliary route. Gallbladder had the highest radiation exposure (21 µSv/MBq), and the effective dose was 4.3 µSv/MBq. Conclusion 11C-NOP-1A is a promising radioligand that reliably quantifies NOP receptors in human brain. The effective dose in humans is low and similar to that of other 11C-labeled radioligands, allowing multiple scans in 1 subject.

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“…To date, anatomic evidence for the different OR subtypes in the human heart has been scarce. Most investigators have confirmed the presence of DOR mRNA and protein, but there is still conflicting evidence for MOR and KOR [18][19][20]. Moreover, immunohistochemical studies of their anatomic distribution are lacking.…”

Section: Introductionmentioning

confidence: 99%

The presence of mu-, delta-, and kappa-opioid receptors in human heart tissue

et al. 2014

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Functional evidence suggests that the stimulation of peripheral and central opioid receptors (ORs) is able to modulate heart function. Moreover, selective stimulation of either cardiac or central ORs evokes preconditioning and, therefore, protects the heart against ischemic injury. However, anatomic evidence for OR subtypes in the human heart is scarce. Human heart tissue obtained during autopsy after sudden death was examined immunohistochemically for mu- (MOR), kappa- (KOR), and delta- (DOR) OR subtypes. MOR and DOR immunoreactivity was found mainly in myocardial cells, as well as on sparse individual nerve fibers. KOR immunoreactivity was identified predominantly in myocardial cells and on intrinsic cardiac adrenergic (ICA) cell-like structures. Double immunofluorescence confocal microscopy revealed that DOR colocalized with the neuronal marker PGP9.5, as well as with the sensory neuron marker calcitonin gene-related peptide (CGRP). CGRP-immunoreactive (IR) fibers were detected either in nerve bundles or as sparse individual fibers containing varicose-like structures. Our findings offer the first hint of an anatomic basis for the existence of OR subtypes in the human heart by demonstrating their presence in CGRP-IR sensory nerve fibers, small cells with an eccentric nucleus resembling ICA cells, and myocardial cells. Taken together, this suggests the role of opioids in both the neural transmission and regulation of myocardial cell function.

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Assessment of nociceptin/orphanin FQ and μ-opioid receptor mRNA in the human right atrium

Abstract: The human right atrium of patients with coronary artery disease and heart failure expresses mRNA encoding NOP and possibly low levels of MOP. This does not correlate with degree of cardiac dysfunction. In addition, the atrium does not express ppN/OFQ mRNA.

Cited by 17 publications

References 31 publications

Role of endogenous opioid peptides in the infarct size-limiting effect of adaptation to chronic continuous hypoxia

Role of endogenous opioid peptides in the infarct size-limiting effect of adaptation to chronic continuous hypoxia

Brain and Whole-Body Imaging of Nociceptin/Orphanin FQ Peptide Receptor in Humans Using the PET Ligand ¹¹C-NOP-1A

The presence of mu-, delta-, and kappa-opioid receptors in human heart tissue

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Assessment of nociceptin/orphanin FQ and μ-opioid receptor mRNA in the human right atrium

Abstract: The human right atrium of patients with coronary artery disease and heart failure expresses mRNA encoding NOP and possibly low levels of MOP. This does not correlate with degree of cardiac dysfunction. In addition, the atrium does not express ppN/OFQ mRNA.

Cited by 17 publications

References 31 publications

Role of endogenous opioid peptides in the infarct size-limiting effect of adaptation to chronic continuous hypoxia

Role of endogenous opioid peptides in the infarct size-limiting effect of adaptation to chronic continuous hypoxia

Brain and Whole-Body Imaging of Nociceptin/Orphanin FQ Peptide Receptor in Humans Using the PET Ligand 11C-NOP-1A

The presence of mu-, delta-, and kappa-opioid receptors in human heart tissue

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Brain and Whole-Body Imaging of Nociceptin/Orphanin FQ Peptide Receptor in Humans Using the PET Ligand ¹¹C-NOP-1A