Kinetic evidence for cytoplasmic calcium as an inhibitory messenger in parathyroid hormone release.
A sudden change of extracellular Ca2+ from 0.5 to 3.0 mM resulted in a transient rise of the cytoplasmic Ca2+ concentration (Ca2+i) followed by a sustained increase in parathyroid cells loaded with the Ca2+-indicator fura-2. The initial transient could be eliminated by increasing the Ca2+ buffering capacity of the cytoplasm. Under such conditions the rise of Ca2+i exhibited kinetics reminiscent of those for 45Ca uptake and cell depolarization. Addition of 0.5 mM Mn2+ mimicked the effect of raising the extracellular Ca2+ concentration, since there was an initial Ca2+i transient followed by a slower entry of Mn2+ into the cells. This reaction pattern was different from that of pancreatic alpha 2-cells in which there was no substantial influx of Mn2+ before depolarization with arginine. When measuring the kinetics of parathyroid hormone (PTH) release it was apparent that Ca2+ inhibition of secretion followed Ca2+i and thus became substantially delayed after eliminating the initial transient. The results support the concept of a depolarizing Ca2+ permeability in the parathyroid cell membrane which can be activated by external Ca2+, and indicate that Ca2+i is an inhibitory messenger of importance for the physiological regulation of PTH release.
Wallfelt
C
C
Department of Surgery, University of Uppsala, Sweden.
Lindh
E
E
Larsson
R
R
Johansson
H
H
Rastad
J
J
Akerström
G
G
Gylfe
E
E
D000818:Animals; D001692:Biological Transport; D002118:Calcium / Q000502:physiology*; D002417:Cattle; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007700:Kinetics; D008345:Manganese / Q000494:pharmacology; D010280:Parathyroid Glands / Q000378:metabolism*; D010281:Parathyroid Hormone / Q000378:metabolism*
D010281:Parathyroid Hormone; D008345:Manganese; D002118:Calcium