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Presence of pituitary adenylate cyclase activating polypeptide-38 in human plasma and milk

Departments of¹ Pharmacology and Pharmacotherapeutics² Biochemistry and Medical Chemistry³ Anatomy⁴ Obstetrics and Gynaecology, University of Pecs, Szigeti u 12, 7624 Pecs, Hungary⁵ Department of Pharmacology and Pharmacotherapeutics, University of Debrecen, 4010 Debrecen, Hungary

(Correspondence should be addressed to D Reglodi; Email: dora.reglodi{at}aok.pte.hu)

^* (R Borzsei and L Mark, as well as Z Helyes and D Reglodi made equal contributions to this work)

Objective: Pituitary adenylate cyclase activating polypeptide (PACAP) is a pleiotropic and multifunctional neuropeptide widely distributed throughout the body. It is involved in the regulation of various physiological and pathophysiological processes, such as reproduction, thermoregulation, motor activity, brain development, neuronal survival, inflammation and pain. Since little is known about its distribution in humans, our aim was to examine PACAP-38 in human plasma. Furthermore, based on the presence of vasoactive intestinal peptide, structurally the closest to PACAP, in milk and PACAP and its receptors in the mammary gland, our aim was to study PACAP-38 in human milk.

Design and methods: The presence of PACAP-38 was determined by mass spectrometry in plasma samples from healthy male and female volunteers (age: 20–40), as well as in plasma and milk samples from lactating women (age: 20–35). PACAP concentration was measured with a specific and sensitive RIA.

Results: Our results revealed that PACAP-38 is present in human plasma, its concentration is relatively stable in healthy volunteers and it is not significantly altered by gender, age, food intake or hormonal cycle in females. However, PACAP-38 plasma levels significantly increased in lactating women having 1–6 month-old babies. Moreover, this study is the first which provides evidence for the presence of PACAP-38 in the human milk with levels 5–20-fold greater in the milk whey than in the respective plasma samples.

Conclusions: We found PACAP-38 in human plasma and its increase during the first 6 months of the lactation period. A prominent, nearly 10-fold higher concentration of this peptide was detected in human milk. Based on the literature, several important actions of milk-derived PACAP-38 can be suggested such as mammary gland proliferation, nutrient transfer as well as regulation of growth/differentiation of certain tissues of the neonates. The novelty of the present descriptive data provides a basis for further investigations on the mechanism of PACAP-38 secretion in human milk and its functional significance.