Fentanyl Stimulates Atrial Natriuretic Peptide Secretion

The effects of fentanyl on ultrastructure, protein biosynthesis, and trial natriuretic peptide (ANP) secretion were studied in neonatal rat cardiomyocytes (CM). Ventricles from 2-day-old American Wistar rats were digested with 1% collagenase in perfusion buffer. Eight hundred thousand to 1.0 million cells /ml were incubated in tissue culture media, to which fentanyl citrate (Sublimaze®) was added in a dose of 10-50 ng/ml. Fentanyl increased the spontaneous CM beating rate, which became rather fibrillary in nature. Protein biosynthesis also increased in a time-related manner. Simultaneous incubation with naloxone (10-6 M) did not alter the beating rate or protein synthesis. Ultrastructurally, several criteria of myocyte growth were observed: an increase in myofilaments and the appearance of newly formed organized sarcomeres, which were preceded by an increase in the ribosomes and cisternae of rough endoplasmic reticulum, and the appearance of large, adult-type mitochondria with increased matrix granules and long parallel cristae. The latter replaced the elongated thin fetal mitochondria. This was associated with a network of developing sarcoplasmic reticulum and T-tubular system as well as the formation of intercalated discs between the CM. Furthermore, exposure to fentanyl increased ANP immunoreactivity in the culture media while simultaneous incubation with naloxone blocked the effect of fentanyl on ANP secretion. On the other hand, naloxone alone did not alter ANP secretion. Therefore, it could be concluded that fentanyl stimulated protein biosynthesis and ANP secretion as evidenced both biochemically and ultrastructurally. Although the molecular mechanism of ANP secretion by fentanyl is still unclear, yet an opioid receptor mediation could be possible as ANP secretion was blocked by an opioid receptor antagonist (naloxone).