A rat brain atlas of urotensin-II receptor expression and a review of central urotensin-II effects

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Urotensin-II (U-II) is an 11-amino acid cyclic peptide which exerts its actions through a G(q) protein-coupled receptor, UT. Much of the research focus of U-II is as a peptide of the periphery, particularly cardiovascular. Despite this, U-II was originally identified as a neuropeptide, and its expression is broad throughout the central nervous system. This brief review article catalogs the known sites of expression of UT within the CNS in the form of a diagrammatic rat brain atlas. Furthermore, the functional consequences of UT activation within specific brain regions are discussed along with the likely actions of synthetic UT ligands. Areas of high, medium, and low expression include the arcuate, paraventricular, and pedunculopontine tegmental nuclei, respectively. In the arcuate and paraventricular nuclei, where expression is high and moderate, U-II produces a pressor/tachycardic response in the former and a weaker response in the latter. Based on the known pharmacology of UT ligands (and assuming density is the primary determinant of efficacy in this case), we predict a weak response in the arcuate nucleus and possible antagonism of endogenous U-II response in the paraventricular nucleus by a low-efficacy partial agonist. These predicted responses lend themselves to relatively simple experimental verification.