Transplacental transfer of the opioid growth factor, [Met5]-enkephalin, in rats

Placental transfer of the pentapeptide [Met5]-enkephalin, known to function as a growth regulating factor and neuromodulatory agent, was studied in pregnant Sprague-Dawley rats. Using separation by reversed phase high-performance liquid chromatography, and analysis by derivative spectroscopy, [Met5]...

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Bibliographic Details
Published in:Brain research bulletin 2001-06, Vol.55 (3), p.341-346
Main Authors: ZAGON, Ian S, WYLIE, James D, HURST, W. Jeffrey, MCLAUGHLIN, Patricia J
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Chromatography, High Pressure Liquid
Embryology: invertebrates and vertebrates. Teratology
Enkephalin, Methionine - pharmacokinetics
Experimental organogenesis
Female
Fetus - metabolism
Fundamental and applied biological sciences. Psychology
Organogenesis. Physiological fonctions
Placenta - metabolism
Pregnancy
Rats
Rats, Sprague-Dawley
Tissue Distribution
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Summary:Placental transfer of the pentapeptide [Met5]-enkephalin, known to function as a growth regulating factor and neuromodulatory agent, was studied in pregnant Sprague-Dawley rats. Using separation by reversed phase high-performance liquid chromatography, and analysis by derivative spectroscopy, [Met5]-enkephalin was detected in 20-day-old fetal tissue including brain, heart, lung, and kidney. Fetal tissues from pregnant rats given an injection of 40 mg/kg [Met5]-enkephalin on gestation day 20 had markedly elevated levels of peptide within 1 h, indicating the transplacental transfer of this opioid. [Met5]-enkephalin levels were increased from control samples at 1, 2, 4, and 14 h post-injection of peptide, but not at 24 h. Evaluation of breakdown products of [Met5]-enkephalin, along with the related peptide [Leu5]-enkephalin, revealed that elution times differed substantially from [Met5]-enkephalin. These data indicate that [Met5]-enkephalin is present in fetal organs, crosses the placenta, does not appear to be restrictive in organ specificity, and is sustained in fetal tissues at detectable levels for at least 14 h. Given that [Met5]-enkephalin tonically inhibits DNA synthesis in the fetus, these results raise the question of whether an elevated level of this peptide (either maternally or from the fetus) may be detrimental to cellular ontogeny in the fetus, and perhaps have long-term implications for postnatal development.
ISSN:0361-9230
1873-2747
DOI:10.1016/S0361-9230(01)00518-4