Evidence that the action of calcitonin on rat osteoclasts is mediated by two G proteins acting via separate post-receptor pathways.
Calcitonin inhibits osteoclastic bone resorption and its action involves two separate acute effects on the osteoclast, both essential to the action of the hormone: abolition of cell motility (Q) and marked cellular retraction (R). The former was mimicked by dibutyryl cyclic AMP and cholera toxin and the latter by pertussis toxin, ionomycin and increases in ambient calcium. Aluminium fluoride ions produced both Q and R effects, while lithium prevented both. In addition, calcitonin elicited a biphasic elevation of cytosolic-free calcium in single isolated osteoclasts. We propose that the action of calcitonin is mediated by at least two G proteins, one responsible for the Q effect and the other for the R effect. In addition, two second messengers, cyclic AMP and calcium, are involved. These findings may help to explain the potency of calcitonin in inhibiting bone resorption, and may allow the rational design of new therapeutic agents designed to alter osteoclast behaviour.
Zaidi
M
M
Department of Cellular and Molecular Sciences, St George's Hospital Medical School, London.
Datta
H K
HK
Moonga
B S
BS
MacIntyre
I
I
D000535:Aluminum / Q000494:pharmacology; D017607:Aluminum Compounds; D000818:Animals; D001862:Bone Resorption / Q000378:metabolism*; D003994:Bucladesine / Q000494:pharmacology; D002116:Calcitonin / Q000494:pharmacology / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D002772:Cholera Toxin / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D003600:Cytosol / Q000378:metabolism; D005459:Fluorides / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000378:metabolism*; D015759:Ionomycin / Q000494:pharmacology; D008094:Lithium / Q000494:pharmacology; D010010:Osteoclasts / Q000187:drug effects / Q000378:metabolism*; D037342:Pertussis Toxin; D051381:Rats; D011919:Rats, Inbred Strains; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D017607:Aluminum Compounds; D010566:Virulence Factors, Bordetella; D005576:Colforsin; D015759:Ionomycin; D003994:Bucladesine; D002116:Calcitonin; D002772:Cholera Toxin; D008094:Lithium; D000535:Aluminum; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D005459:Fluorides; D002118:Calcium; C032311:aluminum fluoride