Expression of Opioid Receptor Subtypes and Their Ligands in Fibrillating Human Atria

Abstract

The delta- and kappa-receptor subtypes are both abundantly expressed in the human heart and participate in age- and stress-related alterations of cardiac function. Opioid receptor agonists mediate cardioprotection in response to ischemic preconditioning via increased intracellular Ca(2) (+) levels, opening mitochondrial K(ATP) channels, and PKC activation. We studied the expression of opioid receptor subtypes kappa and delta, and of their ligand precursors, proopiomelanocortin (POMC) and preproenkephalin A (PENKA), in human atrial tissue of patients in sinus rhythm (SR), or persistent atrial fibrillation (AF). The mitochondrial size was also compared between the two groups. The atrial mRNA expression of opioid peptide precursors and receptors was assessed by competitive and real-time RT-PCR in 16 patients in AF and 16 patients in SR. Mitochondria were analyzed in the atrial tissue by electron microscopy in four patients in AF and four patients in SR. Both PENKA (SR: 100 +/- 33% vs AF: 33 +/- 21%; P < 0.05) and kappa-receptor mRNA amounts (AF: 78 +/- 20% vs SR: 100 +/- 11%; P < 0.05) were both decreased in AF in comparison to SR. In addition, POMC mRNA levels were decreased in AF (SR: 100 +/- 54% vs AF: 37 +/- 26%; P < 0.05), whereas the expression of the corresponding delta-opioid receptor was unchanged (AF: 102 +/- 34% vs 100 +/- 44%). Mitochondrial size was increased during persistent AF. Persistent AF is associated with the down-regulation of the opioid receptor/ligand expression. This suggests a loss of protective capacity in the fibrillating atrial tissue, resulting in an ultrastructural remodeling of atrial myocytes.