Parathyroid hormone is able to enhance cyclic adenosine monophosphate formation without causing an increase in cytoplasmic Ca2+ in osteoblasts.
There are several reports indicating that parathyroid hormone (PTH), besides inducing the formation of cyclic adenosine monophosphate (cAMP), also causes an increase in cytoplasmic free Ca2+ ([Ca2+]i) in osteoblasts, and it has been speculated that both of these second messengers are necessary to mediate PTH-induced bone resorption. In the osteoblastic cell line MC3T3-E1, bovine PTH 1-34 (10 nmol/l-1 mumol/l) stimulated cAMP formation but did not cause an increase in [Ca2+]i in adherent single cells (basal [Ca2+]i = 151 +/- 5 nmol/l, mean +/- SEM; N = 98). In contrast, subsequent addition of bradykinin (1 mumol/l) resulted in a transient increase in [Ca2+]i from a basal level of 155 +/- 11 nmol/l to a peak value of 351 +/- 60 nmol/l (N = 14). When the PTH challenge was followed by the addition of thrombin (10 U/ml), the latter induced a transient rise in [Ca2+]i from a basal level of 173 +/- 12 nmol/l to a peak at 341 +/- 33 nmol/l (N = 20). Primary cultures of human osteoblasts were obtained from trabecular bone. These cells were also PTH-responsive in terms of cAMP formation. On the other hand, human PTH 1-34 (100 nmol/l) did not affect [Ca2+]i in the isolated human osteoblasts, while bradykinin (1 mumol/l) caused a transient increase in [Ca2+]i (from a basal value of [Ca2+]i at 154 +/- 10 nmol/l to a peak value of 757 +/- 147 nmol/l within 30 s; N = 16).(ABSTRACT TRUNCATED AT 250 WORDS)
Ljunggren
O
O
Department of Internal Medicine, University Hospital, Uppsala, Sweden.
Johansson
H
H
Ridefelt
P
P
Lerner
U H
UH
Lindh
E
E
Johansson
A G
AG
Ljunghall
S
S
D001920:Bradykinin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D000242:Cyclic AMP / Q000096:biosynthesis*; D006801:Humans; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism*; D012516:Osteosarcoma / Q000378:metabolism; D010281:Parathyroid Hormone / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D019379:Teriparatide; D013917:Thrombin / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D010281:Parathyroid Hormone; D010446:Peptide Fragments; D019379:Teriparatide; D000242:Cyclic AMP; D013917:Thrombin; D001920:Bradykinin; D002118:Calcium