Expression Of K-opioid Receptor And Its Ligand In Human Fibrillating Atria

Background:Opioid peptides, derived from the three precursor proteins preproenkephalin A (PENKA), preproenkephalin B (PENKB), and pre-pro-opiomelanocortin(POMC) by limited proteolysis in a tissue-specific manner, modify cardiac function in healthy individuals by specifically binding to opioid receptors. Opioid peptides can reach the heart via the systemic circulation when released from the central nervous system or upon the release from the peripheral nerve ending in the cardiac tissue itself. In addition , cardiac tissue, and isolated cardiac myocytes contain PENKA, PENKB,and POMC mRNAs with significant amount of their peptide products including enkephalins, dynorphins, and endorphin. A number of physiologic stimuli and pathologic conditions such as, among others, myocardial ischemia and hypertension, result in profound changes of the cardiac opioid system and related cardiac functions. Whether opioid peptides act directly on the myocardium rather than affect neurotransmitter release remains unclear. A growing body of evidence points to the expression of opioid receptor subtypes in myocytes within the ventricle and atrium, and all subtype-selective opiate receptor agonists have effects on the heart. The EOP and opioid peptide receptors in heart may function during the occurrence and the development of cardiac diseases. Activation of the opioid system seems to increase the resistance against oxidative stress and ischemia. Currently the study of receptors and signal transduction has been becoming the important trend of arrhythmia. Atrial fibrillation is one of the most common arrhythmia in old people and has been a serious threat to public health. The occurrence and maintenance if atrial fibrillation is relevant to the change of structure, function and electrophysiology in heart(the remodeling of heart ), although the pathogenesy remains unclear. So clarifying the relationship between opioid peptide receptor and atrial fibrillation would further the understanding to the pathogenesy of atrial fibrillation .Objective:To study the effects of atrial fibrillation on the expression ofκ- receptor and protein.Methods:RT-PCR, immunohistochemistry and electron microscope were used to compare the mRNA and protein expression ofκ-receptor in human atrial tissue in 24 atrial fibrillation patients (AF) or 24 sinus rhythm patients (SR).Results:Compared with the group of SR,theκ- receptor mRNA amounts [(262±20)vs(196±11),P<0.05]and protein expression [(2325±131)vs(1261±90),P<0.05]in AF was decreased。the average size of mitochondria swells significantly[(1.0±0.15μm)vs(0.8±0.2μm),P<0.05]。Conclusion: The decrease ofκ-receptor mRNA and protein suggests certain protective capacity in the persistent fibrillating atrial tissue was reduced. The significant swelling of the average size of mitochondria is possible a representation of ultramicrostructure remodeling in cardiac atrium cell。...