Actions of parathyroid hormone-related protein on the renal glomerulo-vascular bed

Abstract

Parathyroid hormone (PTH)-related protein (PTHrP) is the main factor responsible for the syndrome of humoral hypercalcemia of malignancy. In addition, PTHrP is produced by a multitude of normal as well as malignant cells and exerts both classic PTH-like and PTH-unlike effects despite limited sequence homology between the two peptides. Thereby, PTHrP has been detected in a wide variety of smooth muscle, both of vascular and nonvascular origin, under normal physiological conditions and exhibits potent smooth muscle relaxation especially in vessels by interacting with PTH receptors supporting the possibility that PTHrP act in an autocrine or paracrine fashion to regulate vascular tone. These observations have prompted intense inquiry into its biological function in this tissue area. The present review focusses on what we know about PTHrP actions and mechanisms of actionin vitro andin vivo in a special vascular bed, namely the intra-renal vascular, where PTHrP has been shown to be expressed.In vitro, PTHrP and PTH bind to glomerular arterioles and tubules in a sanrable and specific manner by interacting with single-class common receptors and stinulate adenylyl cyclase (AC) activity. PTHrP also stimulates AC activity in glomeruli by interaction with PTH receptors. Furthermore, PTHrP, like PTH, vasodilates isolated afferent and efferent arterioles and perfused kidney by nitric oxide-dependent and independent pathways and stimulates directly renal renin release.In vivo, localization of PTH/PTHrP dilatory effects along the renal arterial tree has been investigated on the split hydronephrotic rat kidney showing that peptides specifically and markedly dilate the preglomerular side and thas an efferent dilation is masked by preglomerular production of amgiotensin II through PTHrP-induced renin release. These properties of PTHrP with the recently discovered presence of PTHrP in glomeruli and afferent arteriole argument favorably a role for this peptide as a vascular relaxant and filtration regulator in kidney, yet a thorough understanding of its role in normal renovascular homeostasis will require further investigation.