Guanine nucleotides are potent secretagogues in permeabilized parathyroid cells.

We studied the effects of GTP and its' analogues on PTH release in permeabilized parathyroid cells to assess their role in mediating the unusual inverse relationship between Ca2+ and PTH release in intact parathyroid cells. Both 10-5 M GppNHp and GTP gamma S, nonhydrolysable analogues of GTP, produce up to an 8-fold enhancement of PTH release, which is dose-dependent. This effect is specific for GTP analogues as we could not mimic it with other nucleotides. 10(-3) M GDP beta S, a nonhydrolysable GDP analogue, completely abolishes GppNHp-stimulated hormone release, providing further support for mediation of this effect by a guanine-nucleotide regulatory protein. In GppNHp-stimulated cells, PTH release is maximal at free [Ca2+] less than 200 nM and progressively decreases as the free [Ca2+] increases from 300 nM to 100 microM. These results suggest the presence of a guanine-nucleotide binding protein in the parathyroid cell that may play an important role in the regulation of PTH secretion by Ca2+ and perhaps other secretagogues.