Effects of N-terminal, midregion, and C-terminal parathyroid hormone-related peptides on adenosine 3',5'-monophosphate and cytoplasmic free calcium in rat aortic smooth muscle cells and UMR-106 osteoblast-like cells.

• DOI: 10.1210/endo.133.6.8243262
• Publication Date: 2014-01-08T16:06:00Z
• Authors: S Wu; C J Pirola; J Green; D T Yamaguchi; K Okano; H Jueppner; J S Forrester; J A Fagin; T L Clemens
• Keywords: Parathyroid hormone-related protein; Cyclic adenosine monophosphate; Second messenger system; Calcium in biology

N-Terminal analogs of PTH-related protein (PTHrP) and PTH bind to a common receptor exhibit similar biological properties. However, recent studies suggest that certain midregion C-terminal PTHrP peptides have activities distinct from those in the placenta osteoclasts, respectively. In this study we determined full-length recombinant PTHrP-(1-141) several synthetic N-terminal, midregion, fragments two PTHrP-producing cell types. Peptides were tested for their ability stimulate cAMP production raise intracellular free calcium ([Ca2+]i) primary rat aortic smooth muscle cells (VSMC) UMR-106 osteoblast-like (UMR) cells. UMR PTHrP-(1-34)NH2, PTHrP-(1-141), bovine PTH-(1-34) all increased (approximately 50 fold) [Ca2+]i (180 nM). By contrast, VSMC, these N-terminal (3-fold) but had no detectable effect on [Ca2+]i. PTHrP-(1-34) significantly blunted angiotensin II-induced rise (but not signal) consistent with concept opposes II activity VSMC. PTHrP-(67-86)NH2, PTHrP-(107-138)NH2, PTHrP-(107-111)NH2 either or type. VSMC both expressed 2.5-kilobase PTH/PTHrP messenger RNA (mRNA) transcript. high affinity specific binding 125I-labeled [Tyr36] PTHrP-(1-36)NH2 was detected We conclude PTH-like, N terminus molecule is critical induction pathways cells, stimulation addition, PTHrP, like other established vasodilators, signals mainly (if exclusively) by increasing cAMP.