Spontaneous Intracellular Calcium Oscillations and G^sα Subunit Expression are Inversely Correlated with Secretory Granule Content in Pituitary Cells

Abstract

Cells of the pituitary tumour cell line GH(4) C(1) were exposed to epidermal growth factor, estradiol and insulin for 5 days, a treatment which resulted in 1) increased prolactin storage in secretory granules, 2) the loss of spontaneous [Ca(2+) ](1) oscillations, and 3) a selective reduction of the protein G(s) α, seen in immunoblots, cholera toxin labelling, and vasoactive intestinal peptide stimulation of adenylyl cyclase. In contrast, the glucocorticoid dexamethasone, which increases the expression of G(s) α, partially restored spontaneous [Ca(2+) ](1) oscillations and decreased prolactin storage. It is concluded that G(s) α levels in tumoral cells result in spontaneous electrical activity which may empty prolactin stores by the continuous activation of exocytosis.

Relationships between amplitudes and kinetics of rapid cytosolic free calcium fluctuations in GH4C1 rat pituitary cells: roles for diffusion and calcium-induced calcium release

“…GH4C1 cells are excitable (Taraskevich and Douglas, 1980), containing voltage-gated calcium channels which undergo both spontaneous and inducible (Ozawa and Kimura, 1979;Taraskevich and Douglas, 1980) action potentials mediated by calcium currents. These cells also display spontaneous fluctuations or spikes (Wagner et al, 1993) in [Ca 2]i, and the occurrence of calcium action potentials has been shown to coincide with the initiation of these [Ca 2]i fluctuations (Chiavaroli et al, 1992). The spontaneous calcium spikes are asymmetric, having rising phases which last -0.5 s, and falling phases with mean duration of 1.7 s (K. Brady, unpublished observations).…”