Calcium inflow in cells transfected with cloned rat and porcine calcitonin receptors.
Ca2+ fluxes were examined in HEK 293 cells stably expressing the rat or porcine calcitonin receptors (CTRs). Calcitonin (CT) rapidly increased cytosolic Ca2+ ([Ca2+]i) concentrations in these cells in a manner which was sustained in the presence of extracellular Ca2+ ([Ca2+]e). In cells pretreated with CT, elevation of the [Ca2+]e concentration resulted in a further increase in [Ca2+]i which was concentration-dependent with respect to both the concentration of CT and the increment of [Ca2+]e. Untransfected cells, cells transfected with vector alone, and CTR-transfected cells not treated with CT, were unresponsive to [Ca2+]e. The microsomal Ca(2+)-ATPase inhibitor thapsigargin was able to mimic both the acute [Ca2+]i fluxes and responsiveness to [Ca2+]e mediated by CT in these cells. The CT-induced responsiveness to [Ca2+]e was neither mimicked by, nor affected by, activators of the cAMP or protein kinase C pathways. Treatment of cells with pertussis toxin influenced neither the primary Ca2+ fluxes in response to CT or thapsigargin nor the agonist-induced [Ca2+]e influx. Nifedipine failed to block responses to either CT or thapsigargin. These results lead to the important conclusion that the CTR participates in receptor-activated Ca2+ inflow, in which depletion of intracellular Ca2+ pools leads secondarily to influx of extracellular Ca2+.
Findlay
D M
DM
St Vincent's Institute of Medical Research, Fitzroy, Victoria, Australia.
Houssami
S
S
Sexton
P M
PM
Brady
C L
CL
Martin
T J
TJ
Myers
D E
DE
D000818:Animals; D002116:Calcitonin / Q000378:metabolism / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D018014:Gene Transfer Techniques; D006801:Humans; D017136:Ion Transport; D051381:Rats; D018003:Receptors, Calcitonin / Q000235:genetics / Q000378:metabolism*; D013552:Swine; D013729:Terpenes / Q000494:pharmacology; D019284:Thapsigargin
D018003:Receptors, Calcitonin; D013729:Terpenes; D019284:Thapsigargin; D002116:Calcitonin; D002118:Calcium