“Liberation” of urotensin II from the teleost urophysis: An historical overview

During the past 20 years, urotensin II (UII) has progressed from being a peptide synthesized only in the urophysis of the caudal neurosecretory system of teleost fish to being considered an important physiological regulator in mammals with implications for the pathogenesis of a range of human cardiovascular and renal diseases. The “liberation” of UII from the urophysis was a gradual process and involved the sequential realization that (a) UII is present not only in the urophysis but also in the central nervous systems (CNS) of teleosts, (b) UII peptides, similar in structure to the urophysial peptides, are present in the diffuse caudal neurosecretory systems and/or CNS of species less evolutionarily advanced than teleosts, including Agnatha, thereby showing that UII is a phylogenetically ancient peptide, (c) UII is present in the brain and spinal cord of a tetrapod, the green frog Rana ridibunda, and (d) the UII gene and its specific receptor (GPR14/UT) are expressed in the CNS and certain peripheral tissues of mammals, including the human. The discovery that the genomes of mammals contain an additional gene encoding a UII-related peptide (URP) and the availability of highly effective peptide and non-peptide antagonists to investigate the role of UII in human physiology and pathophysiology ensure that the peptide will remain “center stage” for several years to come.