Forskolin augments the effects of calcitonin on cytoplasmic spreading of isolated rat osteoclasts and plasma calcium levels in the rat.
Recently we have shown that forskolin acts synergistically with calcitonin on stimulation of cyclic AMP (cAMP) production in isolated rat osteoclasts and now show that forskolin also augments later physiological responses to calcitonin. The sensitivity of calcitonin inhibition of cytoplasmic spreading in isolated rat osteoclasts was increased 3.5-fold by simultaneous treatment with 10(-7) M forskolin, which alone had no effect on the response. In weanling rats the threshold of the hypocalcemic response to salmon calcitonin was reduced fivefold by simultaneous treatment with 200 micrograms/kg forskolin i.v., which alone did not influence the plasma calcium. These results provide further evidence that calcitonin-induced inhibition of osteoclast function is mediated by elevation of cAMP levels and suggest that forskolin could be used to augment the therapeutic effects of calcitonin.
Nicholson
G C
GC
University of Melbourne, Department of Medicine, Repatriation General Hospital, Heidelberg, Australia.
Yumita
S
S
Moseley
J M
JM
Yates
A J
AJ
Martin
T J
TJ
D000818:Animals; D000831:Animals, Newborn; D002116:Calcitonin / Q000494:pharmacology*; D002118:Calcium / Q000097:blood*; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology*; D003593:Cytoplasm / Q000187:drug effects / Q000648:ultrastructure; D004357:Drug Synergism; D010010:Osteoclasts / Q000166:cytology* / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values
D005576:Colforsin; D002116:Calcitonin; D002118:Calcium