ABSTRACT
The importance of combining studies across vertebrates to provide insights into the functionality of hormone systems is considered, using recent advances in Urotensin II (UII) biology to illustrate this. The impact of genome analyses on understanding ligand and UII receptor (UT) structures is reviewed, noting their high conservation from fish to mammals. The early linkage of UII with fish osmoregulatory physiology drove our investigation of possible renal actions of UII in mammals. The kidney is a potential major source of UII in mammals and endogenous peptide appears to have tonal influence over renal excretion of water and electrolytes. Blockade of UII actions by administration of UT receptor antagonist, urantide, in anaesthetised rats, indicates that endogenous UII lowers renal filtration rates and excretion of water and ions. These effects are considered in relation to apparent association of UII with a number of human cardiovascular and renal disorders. Following up the sequencing of UT in mammals here we contrast the first fish UT sequences with those in other species. It is now evident that UT expression in fish osmoregulatory tissues, such as the gill and kidney, exhibits considerable plasticity in response to physiological challenge, providing an important component of the adaptive organismal responses. A number of areas of UII research, which will continue to benefit from moving questions between appropriate vertebrate groups, have been highlighted. These comparative approaches will yield improved understanding and further novel actions of this intriguing endocrine and paracrine system, so highly conserved across the vertebrate series.
Subject(s)
Endocrinology/methods , Urotensins/physiology , Animals , Gene Expression Profiling , Humans , Peptide Fragments/pharmacology , Receptors, G-Protein-Coupled/antagonists & inhibitors , Receptors, G-Protein-Coupled/metabolism , Receptors, G-Protein-Coupled/physiology , Urotensins/genetics , Urotensins/metabolism , Urotensins/pharmacology , Water-Electrolyte Balance/drug effects , Water-Electrolyte Balance/physiologyABSTRACT
Urotensin II (UII) is a potent vasoactive hormone in mammals. However, despite its well-known effects on epithelial sodium transport in fish, little is known about its actions on the mammalian kidney. The aim of this study was to determine the effects of UII on renal function in the rat. Using standard clearance methods, the effects of rUII and the rat UII receptor (UT) antagonist, urantide, were studied. UII was measured in plasma and urine by radioimmunoassay. UII and UT were localized in the kidney by immunohistochemistry and mRNA expression quantified. Rat urinary [UII] was 1,650-fold higher than that in plasma. Immunoreactive-UII was localized to the proximal tubules, outer and inner medullary collecting ducts (IMCD); UT receptor was identified in glomerular arterioles, thin ascending limbs, and IMCD. UII and UT mRNA expression was greater in the medulla; expression was higher still in spontaneously hypertensive rats (SHRs) associated with raised plasma (UII). Injection of rUII induced reductions in glomerular filtration rate (GFR), urine flow, and sodium excretion. Urantide infusion resulted in increases in these variables. Endogenous UII appears to contribute to the regulation of GFR and renal sodium and water handling in the rat. While hemodynamic changes predominate, we cannot rule out the possibility of a direct tubular action of UII. Increased expression of UII and UT in the SHR suggests that UII plays a role in the pathophysiology of cardiovascular disease.
