title: Cellular localization and adaptive changes of the cardiac delta opioid receptor system in an experimental model of heart failure in rats.
abstract: The role of the cardiac opioid system in congestive heart failure (CHF) is not fully understood. Therefore, this project investigated the cellular localization of delta opioid receptors (DOR) in left ventricle (LV) myocardium and adaptive changes in DOR and its endogenous ligand, the precursor peptide proenkephalin (PENK), during CHF. Following IRB approval, DOR localization was determined by radioligand binding using [H(3)]Naltrindole and by double immunofluorescence confocal analysis in the LV of male Wistar rats. Additionally, 28 days following an infrarenal aortocaval fistula (ACF) the extent of CHF and adaptions in left ventricular DOR and PENK expression were examined by hemodynamic measurements, RT-PCR, and Western blot. DOR specific membrane binding sites were identified in LV myocardium. DOR were colocalized with L-type Ca(2+)-channels (Cav1.2) as well as with intracellular ryanodine receptors (RyR) of the sarcoplasmatic reticulum. Following ACF severe congestive heart failure developed in all rats and was accompanied by up-regulation of DOR and PENK on mRNA as well as receptor proteins representing consecutive adaptations. These findings might suggest that the cardiac delta opioid system possesses the ability to play a regulatory role in the cardiomyocyte calcium homeostasis, especially in response to heart failure.
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Campus Charité Mitte and Campus Virchow Klinikum, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany. sascha.treskatsch@charite.de.
authors.forename: Sascha
authors.initials: S
authors.lastname: Treskatsch
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Campus Charité Mitte and Campus Virchow Klinikum, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany. aarne.feldheiser@charite.de.
authors.forename: Aarne
authors.initials: A
authors.lastname: Feldheiser
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Campus Charité Mitte and Campus Virchow Klinikum, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany. mohammed.shaqura@charite.de.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Shaqura
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Campus Charité Mitte and Campus Virchow Klinikum, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany. lukas.dehe@charite.de.
authors.forename: Lukas
authors.initials: L
authors.lastname: Dehe
authors.affiliation: Institute of Physiology, Campus Charité Mitte, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany. helmut.habazettl@charite.de.
authors.forename: Helmut
authors.initials: H
authors.lastname: Habazettl
authors.affiliation: Department of Cardiology, Campus Charité Mitte, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany. torsten.roepke@charite.de.
authors.forename: Torsten K
authors.initials: TK
authors.lastname: Röpke
authors.affiliation: Institute of Anatomy, Ludwig-Maximilians-Universität München, Pettenkoferstraße 11, 80336, Munich, Germany. mehdi.shakibaei@med.uni-muenchen.de.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Shakibaei
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Campus Charité Mitte and Campus Virchow Klinikum, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany. micha.schaefer@charite.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Schäfer
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Campus Charité Mitte and Campus Virchow Klinikum, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany. claudia.spies@charite.de.
authors.forename: Claudia D
authors.initials: CD
authors.lastname: Spies
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Campus Charité Mitte and Campus Virchow Klinikum, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany. shaaban.mousa@charite.de.
authors.forename: Shaaban A
authors.initials: SA
authors.lastname: Mousa
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D001667:Binding, Competitive; D020746:Calcium Channels, L-Type / Q000378:metabolism; D004195:Disease Models, Animal; D004745:Enkephalins / Q000235:genetics / Q000378:metabolism*; D006333:Heart Failure / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D008024:Ligands; D008297:Male; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009271:Naltrexone / Q000031:analogs & derivatives / Q000378:metabolism; D011485:Protein Binding; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism*; D011869:Radioligand Assay; D017208:Rats, Wistar; D017465:Receptors, Opioid, delta / Q000235:genetics / Q000378:metabolism*; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism; D013318:Stroke Volume; D016277:Ventricular Function, Left
chemical_list: D020746:Calcium Channels, L-Type; D004745:Enkephalins; C419385:L-type calcium channel alpha(1C); D008024:Ligands; D011498:Protein Precursors; D017465:Receptors, Opioid, delta; D019837:Ryanodine Receptor Calcium Release Channel; C029992:proenkephalin; D009271:Naltrexone; C055382:naltrindole
keywords: Aortocaval fistula; Delta opioid receptor; Heart failure; Proenkephalin