Inhibition by Calcium of the Cyclic AMP-Mediated Stimulation of Thymic Lymphoblast Proliferation by Prostaglandin E₁ [*]

Abstract

During the first 10 min after exposure of rat thymic lymphocytes (thymocytes) to a high concentration (5.0 µg/ml) of prostaglandin E₁ (PGE₁) in medium without added calcium, there is a 67-fold rise in the cellular cyclic AMP content which causes strong stimulations of deoxyribunucleic acid (DNA) synthesis and cell proliferation. On the other hand, in the presence of 1.0 mM calcium, PGE₁ causes a similar (68-fold) rise in the cellular cyclic AMP content and a strong stimulation of DNA synthesis, but the stimulated cells do not enter mitosis. Thus, calcium selectively inhibits the cyclic AMP-induced mitogenic process.

The calcium-sensitive phase of the mitogenic reaction is normally completed by only 2.5 min after exposure to PGE₁; addition of calcium to the extracellular fluid at, or after, this time does not inhibit the flow of stimulated cells into mitosis which begins between 3 and 4 hr later. Finally, calcium must inhibit the operation, but not the cyclic AMP-mediated activation, of the mitogenic system since the inhibition can be fully relieved by removal of calcium at least 4 hr after exposure to PGE₁.

Key words

Prostaglandin E₁ - Calcium - DNA Synthesis - Cell Proliferation

1 Issued as NRCC No. 12681

1 Issued as NRCC No. 12681