Abstract 298: Downregulation of Delta and Kappa Opioid Receptors in Post-heart Transplantation in Human and Rats

Abstract

Over the past decade, multiple data regarding local opioid regulation of heart function have been demonstrated. However, opioid receptors (ORs) have not yet characterized in post-heart transplantation. Since a transplanted heart is devoid of innervations and autonomic innervations modulate ORs, we assessed the hypothesis that a possible down-regulation of k-OR and δ-OR in heart transplants. Endomyocardial biopsies were collected in 15 male patients at 30 days of orthotopic heart transplantation and in 15 control male patients during aortic valve surgery in human. Another study performed in 20 heterotopic heart transplants (HHT) and 20 naïve hearts of Sprague-Dawley male rats. The mRNA transcript encoding the Oprd1 and Oprk1, KOR and DOR proteins, distribution, and cellular localization were identified using RT-qPCR, Western blot, IHC, and IF, respectively. Transcripts of mRNA encoding the Oprd1 and Oprk1 were detected in hearts of human and rats. Expression of Oprd1 (p=0.036) and Oprk1 (p = 0.004) was significantly reduced in transplanted hearts. In Western blot analysis, KOR and DOR levels of expression were significantly lowered (p=0.03, KOR; p=0.01, DOR) in HHT compared to naïve hearts in rats. Immunohistochemistry analysis demonstrated a lighter labeling on the distribution of DOR and KOR in heart transplants` tissue in both rats and human. In both species, dual labeling myocardial isoforms (KOR and DOR) co-localized in cardiomyocytes of transplant and control hearts. These findings suggest that the down-regulation of DOR and KOR receptors in hearts transplant of both human and rats might have a possible increased susceptibility to ischemia-reperfusion injury.