PACAP is a multifunctional neuropeptide, with two active forms, PACAP38 and PACAP27. We have previously shown that PACAP is protective in renal ischemia/reperfusion injury, but the peptide itself has not been identified in the rat kidney yet. The first aim of our study was to identify PACAP in the rat kidney using mass spectrometry and radioimmunoassay. PACAP or PACAP-like immunoreactivity was shown by the two methods, respectively.

Previous studies revealed the existence of all 3 PACAP receptors (PAC1, VPAC1 and 2) in the kidney, but their exact localization in histological sections is not known. Since most of the cytoprotective effects of PACAP are related to its specific PAC1 receptor, our second aim was to identify the cell types where PAC1 receptor is expressed in the rat kidney. We detected PAC1 receptor immunoreactivity in the tubular cells with immunohistochemistry.

In other sets of experiments, based on previous studies proving renoprotective effect of PACAP, we have examined changes of endogenous PACAP following 60 min renal ischemia using radioimmunoassay. Changes were observed within 24 hours following renal vessel clamping. In the cortex, an acute decrease was followed by an increase on the intact side and levels returned to original ones on the operated side. In the medulla, changes were only observed on the clamped side: a marked upregulation was detected in PACAP38-like immunoreactivity within the first 24 hours.

In conclusion, our results show that PACAP is endogenously present in the rat kidney, and the tubular localization of PAC1 receptor provides the basis for the renal effects of the peptide under physiological and pathological conditions. Furthermore, the PACAP38- and PACAP27-like immunoreactivities sensitively react to renal ischemia/reperfusion, the physiological importance of which awaits further investigation.

Support by: Grants OTKA K72592, CNK78480, T73044, Bolyai Scholarship, Lendület Program of the Hungarian Academy of Sciences.