TY  - JOUR
AU  - Stern, P H
AU  - Tatrai, A
AU  - Semler, D E
AU  - Suk, Kyeong Lee
AU  - Lakatos, Péter
AU  - Strieleman, P J
AU  - Tarjan, G
AU  - Sanders, J L
TI  - Endothelin receptors, second messengers, and actions in bone
JF  - JOURNAL OF NUTRITION
J2  - J NUTR
VL  - 125
PY  - 1995
IS  - 7 Suppl
SP  - 2028S
EP  - 2032S
PG  - 5
SN  - 0022-3166
UR  - https://m2.mtmt.hu/api/publication/1802369
ID  - 1802369
AB  - Endothelins are a class of peptides that are produced by and elicit responses in many tissues. A growing literature documents the presence and effects of endothelins in bone. Both endothelin(A) and endothelin(B) receptors have been demonstrated in osteoblastic cells by ligand binding. Major signal transduction pathways for endothelin in bone cells appear to be stimulation of phospholipid turnover, by activation of A, C and D phospholipases, stimulation of calcium flux from intracellular and extracellular stores and activation of tyrosine kinases. Endothelins also modulate calcium signaling elicited by other agents in osteoblastic cells. The parathyroid hormone-stimulated calcium transient in GMR-106 cells is enhanced by endothelins, acting through an endothelin(B) receptor, whereas the parathyroid hormone-stimulated increase in cyclic AMP is inhibited by endothelins. Phenotypic responses to endothelin-1 include changes in alkaline phosphatase activity, stimulation of osteocalcin and osteopontin message, stimulation of collagen and noncollagenous protein synthesis, inhibition of osteoclast motility and stimulation of prostaglandin-dependent resorption. Endothelin-1 also enhances the interleukin-1-induced increase in interleukin- 6. Endothelins can also potentially affect calcium metabolism through their actions to inhibit the secretion of parathyroid hormone.
LA  - English
DB  - MTMT
ER  - 

TY  - JOUR
AU  - Tatrai, A
AU  - Lakatos, Péter
AU  - Thompson, S
AU  - Stern, P H
TI  - Effects of endothelin-1 on signal transduction in UMR-106 osteoblastic cells
JF  - JOURNAL OF BONE AND MINERAL RESEARCH
J2  - J BONE MINER RES
VL  - 7
PY  - 1992
IS  - 10
SP  - 1201
EP  - 1209
PG  - 9
SN  - 0884-0431
DO  - 10.1002/jbmr.5650071012
UR  - https://m2.mtmt.hu/api/publication/1802378
ID  - 1802378
N1  - Manufacturers: calbiochem, United States; sigma, United States
Cited By :26            
            Export Date: 11 March 2020            
            Correspondence Address: Tatrai, A.; Department of Pharmacology, Northwestern University Medical School, 303 East Chicago Avenue, Chicago, Illinois, 60611, United States            
            Chemicals/CAS: cyclic AMP, 60-92-4; indometacin, 53-86-1, 74252-25-8, 7681-54-1; Calcium, 7440-70-2; Cyclic AMP, 60-92-4; Endothelins; Inositol Phosphates; Nifedipine, 21829-25-4            
            Manufacturers: calbiochem, United States; sigma, United States
AB  - Endothelin-1 is now recognized to affect the functions of a number of tissues and to activate calcium/phospholipid second messenger pathways in target cells. In the present study, we characterized its effects on signal transduction in UMR-106 cells. To study calcium transients elicited by endothelin-1, cells were loaded either with fluo-3 (for the measurement of cytosolic free calcium) or chlortetracycline (for the measurement of intracellularly stored calcium) as fluorescent probes. Intracellular production of inositol phosphates and cyclic AMP was also measured. Endothelin-1 elicited dose-dependent cytosolic calcium transients with an ED50 of 20 nM. This effect was also seen in EGTA-containing or calcium-free medium; however, the signals were reduced in magnitude. The dihydropyridine calcium channel antagonist nifedipine did not affect the response. Repeated administration of endothelin-1 resulted in homologous desensitization of the response. A 4 minute pretreatment with phorbol ester reduced the initial response to endothelin-1 in both calcium-containing and calcium-free media. A 24 h pretreatment with indomethacin had no effect on response. Using chlortetracycline as an indicator, a significant reduction in intracellularly stored calcium by endothelin-1 was observed. This was prevented by 8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate, a blocker of calcium release from internal stores. Endothelin-1 also stimulated the dose-dependent production of inositol phosphates by UMR-106 cells. Indomethacin was also without effect on this process. The increase in inositol trisphosphates was seen within the same time frame as the increase in cytosolic calcium. Endothelin-1 did not influence cyclic AMP production over 5 minutes in these cells. In conclusion, endothelin-1 has a significant effect on UMR-106 osteoblastic cells to activate the calcium and inositol phosphate second messenger systems. Our findings raise the intriguing question of the physiologic role of endothelin-I in bone metabolism.
LA  - English
DB  - MTMT
ER  -