Differences in intracellular calcium signaling after activation of the thrombin receptor by thrombin and agonist peptide in osteoblast-like cells

Jenkins, Alison L.; Bootman, Martin D.; Berridge, Michael J. and Stone, Stuart R. (1994). Differences in intracellular calcium signaling after activation of the thrombin receptor by thrombin and agonist peptide in osteoblast-like cells. The Journal of Biological Chemistry, 269(25) pp. 17104–17110.

Abstract

Thrombin and the thrombin receptor agonist peptide (TRAP) caused a rise in intracellular calcium concentration ([Ca²⁺]_i) in the human osteoblast-like cell line Saos-2. Striking differences in the [Ca²⁺]_i signals elicited by these agonists were revealed. In cell populations, thrombin induced a transient increase in [Ca²⁺]_i while TRAP caused a biphasic [Ca²⁺]_i response consisting of an initial peak and a sustained plateau phase. In individual cells, thrombin mainly caused a single [Ca²⁺]_i transient while TRAP induced repetitive [Ca²⁺]_i spikes. Neither tyrosine phosphorylation, cAMP-dependent phosphorylation, nor pertussis toxin-sensitive G proteins appeared to be involved in thrombin receptor [Ca²⁺]_isignaling in this cell line. However, the sustained [Ca²⁺]_i response caused by TRAP was converted into a transient, thrombin-like response by pretreatment with serine/threonine phosphatase inhibitors. Pretreatment with the phorbol ester phorbol 12-myristate 13-acetate (PMA) abrogated thrombin receptor [Ca²⁺]_i signaling, and TRAP-induced Ca²⁺ entry was inhibited by the acute treatment with PMA. In contrast, Ca²⁺ entry stimulated by thapsigargin was not sensitive to agents affecting serine/threonine phosphorylation. The observation that thrombin and TRAP, despite being agonists for a common receptor, induce dissimilar [Ca²⁺]_i responses indicates that binding of TRAP alone is insufficient to fully regulate the thrombin receptor in Saos-2 cells.

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