Transplacental transfer of the opioid growth factor, [Met(5)]-enkephalin, in rats

Placental transfer of the pentapeptide [Met(5)]-enkephalin, known to functi on as, a growth regulating factor and neuromodulatory agent, was studied in pregnant Sprague-Dawley rats. Using separation by reversed phase high-perf ormance liquid chromatography, and analysis by derivative spectroscopy, [Me t(5)]-enkephalin was detected in 20-day-old fetal tissue including brain, h eart, lung, and kidney. Fetal tissues from pregnant rats given an injection of 40 mg/kg [Met(5)]-enkephalin on gestation day 20 had markedly elevated levels of peptide within 1 h, indicating the transplacental transfer of thi s opioid. [Met(5)]-enkephalin levels were increased from control samples at 1, 2, 4, and 14 h post-injection of peptide, but not at 24 h. Evaluation o f breakdown products of [Met(5)]-enkephalin, along with the related peptide [Leu(5)]-enkephalin, revealed that elution times differed substantially fr om [Met(5)]-enkephalin. These data indicate that [Met(5)]-enkephalin is pre sent in fetal organs, crosses the placenta, does not appear to be restricti ve in organ specificity, and is sustained in fetal tissues at detectable le vels for at least 14 h. Given that [Met(5)]-enkephalin tonically inhibits D NA synthesis in the fetus, these results raise the question of whether an e levated level of this peptide (either maternally or from the fetus) may be detrimental to cellular ontogeny in the fetus, and perhaps have long-term i mplications for postnatal development. (C) 2001 Elsevier Science Inc.