Effects of parathyroid hormone-related protein on human mesangial cells in culture.
Parathyroid hormone (PTH) and PTH-related protein (PTHrP) produce similar biological effects through the PTH/PTHrP receptor. Because PTHrP exhibits vasodilatory properties, we evaluated the hypothesis that this hormone interacts with human mesangial cells (HMC). The PTHrP prevented both the expected reduction in the planar cell surface area and the increase in myosin light-chain phosphorylation induced by platelet-activating factor (PAF) on HMC, in a dose-dependent manner. This effect was completely blocked by pertussis toxin and dideoxyadenosine, suggesting that a G protein-coupled receptor and cAMP are important in the PTHrP transduction mechanism. Moreover, PTHrP increased cAMP synthesis and thymidine incorporation in HMC. However, whereas RT-PCR and Southern and Northern blot analyses demonstrated the expression of human PTH/PTHrP receptor in human kidney cortex, no expression could be demonstrated in HMC. These results show that PTH and PTHrP directly interact with mesangial cells. These effects might be mediated by a receptor different from the PTH/PTHrP receptor.
Bosch
R J
RJ
Department of Physiology, Alcalá School of Medicine, University of Alcalá," Alcalá de Henares 28871, Spain. ricardoj.bosch@alcala.es
Rojo-Linares
P
P
Torrecillas-Casamayor
G
G
Iglesias-Cruz
M C
MC
Rodríguez-Puyol
D
D
Rodríguez-Puyol
M
M
D000959:Antihypertensive Agents / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D003634:DDT / Q000031:analogs & derivatives / Q000494:pharmacology; D015870:Gene Expression / Q000502:physiology; D005920:Glomerular Mesangium / Q000166:cytology* / Q000187:drug effects*; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics; D018994:Myosin Light Chains / Q000378:metabolism; D010281:Parathyroid Hormone / Q000494:pharmacology*; D044162:Parathyroid Hormone-Related Protein; D037342:Pertussis Toxin; D010766:Phosphorylation; D010972:Platelet Activating Factor / Q000494:pharmacology; D011506:Proteins / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D018016:Receptors, Parathyroid Hormone / Q000235:genetics; D015290:Second Messenger Systems / Q000502:physiology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D000959:Antihypertensive Agents; D008565:Membrane Proteins; D018994:Myosin Light Chains; C470121:PTHLH protein, human; D010281:Parathyroid Hormone; D044162:Parathyroid Hormone-Related Protein; D010972:Platelet Activating Factor; D011506:Proteins; D012333:RNA, Messenger; D018016:Receptors, Parathyroid Hormone; D010566:Virulence Factors, Bordetella; C000849:bis(p-chlorophenyl)acetic acid; D003634:DDT; D000242:Cyclic AMP; D037342:Pertussis Toxin