Letter regarding article by Rademaker et al, "integrated hemodynamic, hormonal, and renal actions of urocortin 2 in normal and paced sheep: beneficial effects in heart failure".

To the Editor: I read with great interest the study by Rademaker et al 1 reporting the beneficial cardiovascular and humoral effects of urocortin 2 in sheep with heart failure induced by pacing. Urocortin 2 is a potent vasodilator peptide that acts specifically on the corticotropin-releasing factor type 2 receptor. The study by Rademaker et al 1 suggests that this peptide may have therapeutic potential in patients with heart failure. However, I would like to remind the readers that the presence of urocortin 2 peptide in human tissues, including the heart, has not been established so far. If human urocortin 2 is not an endogenous peptide, the administration of the authentic peptide may cause allergic responses in human subjects. The complementary DNA coding urocortin 2 was shown to be present in humans, but the predicted human urocortin 2 precursor lacks a consensus proteolytic cleavage site that would allow C-terminal processing of the peptide. 2,3 Initially, it had been referred to as a urocortin-related peptide sequence. Furthermore, no reports are available on the presence of immunoreactive urocortin 2 in human tissues shown by either radioimmunoassay or immunohistochemistry. In contrast, our previous studies have shown the presence of urocortin 1 and urocortin 3 in human heart and other human tissues by means of radioimmunoassay and immunohistochemistry. 4,5 The important issue before the clinical use of this peptide is therefore to clarify whether or not urocortin 2 is an endogenous peptide in humans. This issue could be clarified by studies using radioimmunoassay and immunohistochemistry if a specific uro-cortin 2 antibody is available. Another important issue would be to clarify whether urocortin 3, another specific agonist for corticotropin-releasing factor type 2 receptor, has potent effects on heart failure similar to those found in urocortin 2. 1 Disclosures None. and renal actions of urocortin 2 in normal and paced sheep: beneficial effects in heart failure. II: a member of the corticotropin-releasing factor (CRF) neuropeptide family that is selectively bound by type 2 CRF receptors. Human stresscopin and stresscopin-related peptide are selective ligands for the type 2 corticotropin-releasing hormone receptor. Expression of urocortin and corticotropin-releasing factor receptor subtypes in the human heart. Expression of urocortin III/stresscopin in human heart and kidney. Response We thank Dr Takahashi for his interest in our article. 1 He expresses concern that because there are currently no reports available on the presence of urocortin 2 (Ucn2) immunoreactiv-ity in human tissues, the …