Alterations of pituitary adenylate cyclase-activating polypeptide-like immunoreactivity in the human plasma during pregnancy and after birth.

BACKGROUND: Since its discovery, several distinct effects of pituitary adenylate cyclase activating polypeptide (PACAP) have been established - predominantly in animal studies - in the nervous system, various peripheral organs as well as in the endocrine regulation. It is unknown whether PACAP has any effect on human pregnancy regarding either utero-maternal or perinatal aspects of the gestation. AIM: We investigated alterations of PACAP38-like immunoreactivity (PACAP38-LI) in the human plasma throughout normal pregnancy, during and after delivery, and its level in the umbilical vessels, as well as in the peripheral blood of term healthy newborns. MATERIALS AND METHODS: A 2 ml blood sample was used for each test, PACAP38-LI was determined by radioimmunoassay. RESULTS: In the 2nd and 3rd trimester significant elevation was observed in the PACAP38-LI compared to the earlier gestation and non-pregnant conditions. During delivery its level significantly decreased and returned to the original values 3 days after birth. In the neonates PACAP38-LI level of the peripheral blood was similar to that of healthy adults, but umbilical arteries and veins contained significantly lower concentrations of PACAP38-LI. Besides, the levels were lower in the umbilical vein compared to the artery. CONCLUSIONS: PACAP38-LI levels show sensitive change during normal pregnancy and delivery. Our findings suggest that the fetal organs actively synthesize PACAP. Further investigations are required to elucidate the physiological importance of the alterations observed.

Examination of PACAP38-like immunoreactivity in different milk and infant formula samples.

Pituitary adenylate cyclase activating polypeptide (PACAP) is a neuropeptide with special importance in reproductive and developmental processes. PACAP is found in two bioactive forms: PACAP27 and PACAP38. Recently, we have described that PACAP38 is present in high levels in the milk of human and ruminant animals. Breastfeeding is of utmost importance in proper nutrition of the newborn, but artificial nursing with infant formulas is necessary when breastfeeding is not available. Composition of the breast milk varies during the whole period of nursing and it shows differences at the beginning (foremilk) and the end of an actual suckling (hindmilk). The aim of this study was to investigate PACAP38-like immunoreactivity (PACAP38-LI) in different milk and infant formula samples by radioimmunoassay and to prove the presence of PACAP38 in the infant formula by mass spectrometry. We found similar PACAP38-LI in human mature foremilk and hindmilk samples, in the fresh and pasteurized cow milk and also in formulas. However, we found significantly higher PACAP38-LI in the hypoantigenic formula undergoing extensive hydrolysis compared to the non-hypoantigenic ones. Our results suggest that PACAP38 is relatively stable in the milk and it can withstand the manufacturing processes.

Effect of PACAP treatment on kidney morphology and cytokine expression in rat diabetic nephropathy.

Pituitary adenylate cyclase activating polypeptide (PACAP) is a neuropeptide, exerting diverse effects. One of its frequently examined functions is cell protection, which is achieved mainly via inhibiting apoptotic, inflammatory and oxidative processes. All its three receptors (PAC1, VPAC1, VPAC2) are expressed in the kidney and PACAP has been shown to have protective effects against different renal pathologies. Diabetic nephropathy is the leading cause of end stage renal disease. The aim of the present study was to investigate the possible ameliorative effect of PACAP in streptozotocin-induced diabetic nephropathy and to evaluate its anti-inflammatory effect in this model. Diabetes was induced by a single intravenous injection of streptozotocin (65 mg/kg) in male Wistar rats. PACAP-treated animals were administered ip. 20 µg PACAP every second day, while untreated animals were given vehicle. Kidneys were removed after 8-weeks survival. Besides the complex histological analysis (glomerular PAS positive area/glomerulus area, tubular damage, arteriolar hyalinosis), expression of several cytokines was evaluated by cytokine array and Luminex assay. Histological analysis revealed severe diabetic changes in kidneys of control diabetic animals (glomerular PAS-positive area expansion, tubular damage, Armanni-Ebstein phenomenon). PACAP treatment significantly diminished the damage. Diabetic kidneys showed significant cytokine activation compared to their healthy controls. PACAP was effective in downregulation of several cytokines including CINC-1, TIMP-1, LIX, MIG, s-ICAM. To conclude, PACAP is effective in ameliorating diabetic nephropathy at least partly through its well-known anti-inflammatory effect. These results raise the opportunity for the use of PACAP as a possible therapeutic or preventive method in treating the complications of diabetes.

PACAP immunoreactivity in human malignant tumor samples and cardiac diseases.

Pituitary adenylate cyclase activating polypeptide (PACAP) is a pleiotropic and multifunctional neuropeptide having important roles in various physiological processes. Recent trends in PACAP research point to the clinical introduction of PACAP or its analogs/fragments possibly in the near future. Recently, we have shown the presence of PACAP in human plasma, milk, placenta, and follicular fluid samples. However, relatively few data are available on PACAP in human tissues from patients with different disorders. The aim of the present study was to determine, by radioimmunoassay, the tissue level of PACAP38-like immunoreactivity (LI) and PACAP27-LI in different primary non-small cell lung cancer, colon tumor samples, and in cardiac muscle samples from patients suffering from ischemic heart disease and valvular disorders. We also labeled the PAC1 receptors in human cardiac cells. All samples showed significantly higher PACAP38-LI compared with PACAP27-LI. We found significantly lower levels of PACAP38-LI and PACAP27-LI in tumoral and peripheral samples compared with normal healthy tissue in both lung and colon cancers. Further investigations are necessary to describe the exact function of PACAP in oncogenesis. We showed that PACAP38-LI and PACAP27-LI are significantly higher in ischemic heart diseases compared with valvular abnormalities, suggesting that PACAP might play a role in ischemic heart disorders.