Receptors for pth and pthrp: their biological importance and functional properties. Mannstadt, Michael, Harald J[umlaut]uppner and Thomas J. Gardella. 1Endocrine Unit, Department of Medicine and 2Pediatrics, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA; Tel.: 617-726 3966; Fax: 617-726 7543
APStracts 6:0113F, 1999.
The receptor for parathyroid hormone and parathyroid hormone-related peptide (PTH-1 receptor) is a G protein-coupled receptor that is highly expressed in bone and kidney, and mediates in these tissues the PTH-dependent regulation of mineral ion homeostasis. The PTH-1 receptor also mediates the paracrine actions of PTHrP which play a particularly vital role in the process of endochondral bone formation. These important functions, the likely involvement of the PTH-1 receptor in certain genetic diseases affecting skeletal development and calcium homeostasis, and the potential utility of PTH in treating osteoporosis have been the driving force behind intense investigations of both the receptor and its peptide ligands. Recent lines of work have led to the identification of constitutively active PTH-1 receptors in patients with Jansen's metaphyseal chondrodysplasia, the demonstration of inverse agonism by certain ligand analogs, and the discovery of the PTH-2 receptor subtype, which responds to PTH but not PTHrP. As reviewed herein, a detailed exploration of the receptor-ligand interaction process is currently being pursued through the use of site-directed mutagenesis and photoaffinity crosslinking methods; ultimately, such work could enable the development of novel PTH receptor ligands that have therapeutic value in treating diseases such as osteoporosis and certain forms of hypercalcemia. 

Received 17 May 1999; accepted in final form 11 June 1999.
APS Manuscript Number F125-9.
Article publication pending Am. J. Physiol. (Renal Physiology).
ISSN 1080-4757 Copyright 1999 The American Physiological Society.
Published in APStracts on 22 June 1999