Pertussis toxin inhibits hormonal stimulation of bone resorption in fetal rat limb bones.
The cellular basis for hormonal control of bone resorption is poorly understood. As the identifiable receptors for bone resorbing agents such as parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] are located on osteoblasts rather than osteoclasts, the nature of cellular signaling is obscure. Here it is reported that exposure of fetal rat limb bones to pertussis toxin, a bacterial protein that inhibits certain GTP binding proteins (G-proteins) involved in signal transduction, markedly inhibits bone resorption elicited by PTH, 1,25(OH)2D3 and prostaglandin E2. Pertussis toxin does not block the inhibition of alkaline phosphatase activity by PTH or 1,25(OH)2D3, and it potentiates the cyclic AMP response to PTH. These data support the existence of a pertussis toxin-sensitive G-protein that participates in regulation of bone resorption. The putative G-protein is apparently not involved in the initial transduction of hormonal signals, but it may be part of a final common pathway through which the osteoclast is activated by agents with widely divergent initial actions.
Klein
R F
RF
Department of Medicine, Veterans Administration Medical Center, San Francisco, California.
Nissenson
R A
RA
Strewler
G J
GJ
D000818:Animals; D001862:Bone Resorption / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism; D001842:Bone and Bones / Q000196:embryology / Q000378:metabolism; D002117:Calcitriol / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism; D015232:Dinoprostone / Q000494:pharmacology*; D005121:Extremities; D005333:Fetus; D019204:GTP-Binding Proteins / Q000502:physiology; D005966:Glucuronidase / Q000378:metabolism; D010281:Parathyroid Hormone / Q000494:pharmacology*; D037342:Pertussis Toxin; D051381:Rats; D011919:Rats, Inbred Strains; D013268:Stimulation, Chemical; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D010281:Parathyroid Hormone; D010566:Virulence Factors, Bordetella; D000242:Cyclic AMP; D037342:Pertussis Toxin; D005966:Glucuronidase; D019204:GTP-Binding Proteins; D002117:Calcitriol; D015232:Dinoprostone