URP was discovered in rats when researchers were trying to locate urotensin II (UII), a neuropeptide that is a potent vasoconstrictor and increases REM cycles in the brain. The researchers designed antibodies using Goby UII as an antigen that would target the specific peptide sequence CFWKYC. When the peptide was observed using a mass spectrometer the scientists discovered this peptide was smaller than UII but had similar characteristics as well which is why it was called Urotensin II-related peptide.[1]
Structure
The URP gene is located on the 3q28 chromosome of humans. The mature URP peptide is only 8 peptides long making it smaller than UII. URP is also the same across all vertebrates because it has the same cleaving site unlike UII whose cleaving sites vary among species making its sequence different for all species.[1] URP has the same cysteine bridgedhexapeptide ring with the sequence CFWKYC as UII. This is known as the core and is the major site of action on the peptide. Destruction of the core leads to immediate loss of biological activity.[2] On the other hand, the amino terminus of URP doesn’t seem to contain any relevant information because it can be modified without any loss in pharmacological activity.[3] Unlike UII, URP doesn’t have an acidic amino acid (either glutamic acid or aspartic acid) preceding its core. It is still a potent agonist for the UII- receptor which suggests that this acidic amino acid is not required for activation of the receptor.
Prepro-URP which is the precursor to the mature URP peptide is found in various tissues including specific parts of the brain such as frontal lobe and hypothalamus, and other peripheral tissues such as heart, kidneys, lungs, placenta, ovaries, and testes. In humans the amount of UII and URP gene expression are comparable except in the spinal cord where UII gene expression is much higher.[1]
In rats the UII gene expression is higher than the URP gene expression throughout the entire body. However, when the brains of the rats were tested, only the URP peptide was found making it the primary endogenous ligand in the brain.[1]
Unlike humans and rats, URP gene expression is found in mice spinal cords.[5]
Function
Cardiovascular
When URP is injected into rats a long hypotensive response will be observed.[1] UII is known as a vasoconstrictor meaning that even though both are agonists for the same receptor they can produce opposite effects[6]
Since they are both ligands for the same receptor, an experiment was done to determine which ligand had a higher affinity. When the binding of the two were compared and tested, URP actually had higher affinity.[1]
References
^ abcdefgSugo T, Murakami Y, Shimomura Y, Harada M, Abe M, Ishibashi Y, et al. (October 2003). "Identification of urotensin II-related peptide as the urotensin II-immunoreactive molecule in the rat brain". Biochemical and Biophysical Research Communications. 310 (3): 860–868. doi:10.1016/j.bbrc.2003.09.102. PMID14550283.
^McMaster D, Kobayashi Y, Rivier J, Lederis K (1986). "Characterization of the biologically and antigenically important regions of urotensin II". Proceedings of the Western Pharmacology Society. 29: 205–208. PMID3763612.
^Clark SD, Nothacker HP, Wang Z, Saito Y, Leslie FM, Civelli O (December 2001). "The urotensin II receptor is expressed in the cholinergic mesopontine tegmentum of the rat". Brain Research. 923 (1–2): 120–127. doi:10.1016/s0006-8993(01)03208-5. PMID11743979. S2CID29248060.
^Saetrum Opgaard O, Nothacker H, Ehlert FJ, Krause DN (October 2000). "Human urotensin II mediates vasoconstriction via an increase in inositol phosphates". European Journal of Pharmacology. 406 (2): 265–271. doi:10.1016/s0014-2999(00)00672-5. PMID11020490.
Further reading
Sugo T, Mori M (May 2008). "Another ligand fishing for G protein-coupled receptor 14. Discovery of urotensin II-related peptide in the rat brain". Peptides. 29 (5): 809–812. doi:10.1016/j.peptides.2007.06.005. PMID17628210. S2CID13387250.