Bimatoprost-induced calcium signaling in human T-cells does not involve prostanoid FP or TP receptors

Curr Eye Res. 2009 Mar;34(3):184-95. doi: 10.1080/02713680802669781.

Abstract

Purpose: The prostamide bimatoprost and prostanoid FP receptor agonists are highly efficacious drugs for glaucoma treatment. The presence of both prostamide and prostanoid FP receptors in bimatoprost-sensitive preparations has made prostamide receptor classification difficult. This study investigated a novel bimatoprost-sensitive preparation.

Methods: Human peripheral blood T lymphoblasts (Molt-3) and human osteoblasts (hFOB) were cultured for intracellular calcium signaling studies and quantitative real-time PCR analysis of RNA.

Results: Bimatoprost stimulated concentration-related increases in [Ca(2 +)](i) in a human T-cell line that does not express human FP receptor/variants, according to PCR analysis. The calcium signal induced by bimatoprost was not antagonized by prostanoid FP receptor antagonist/partial agonist AL-8810 or selective TP receptor antagonist SQ 29548. Conversely, bimatoprost did not elevate [Ca(2 +)](i) in human osteoblasts, which were confirmed to contain RNA of human FP receptor/variants.

Conclusions: Molt-3 cells have been identified as a bimatoprost-sensitive preparation in which the activity of bimatoprost is independent of prostanoid FP receptors.

MeSH terms

  • Amides / pharmacology*
  • Antihypertensive Agents / pharmacology*
  • Bimatoprost
  • Calcium / metabolism*
  • Calcium Signaling / drug effects*
  • Cell Proliferation / drug effects
  • Cell Survival
  • Cells, Cultured
  • Cloprostenol / analogs & derivatives*
  • Cloprostenol / pharmacology
  • Dose-Response Relationship, Drug
  • Humans
  • Osteoblasts / metabolism
  • Receptors, Prostaglandin / agonists
  • Receptors, Prostaglandin / antagonists & inhibitors
  • Receptors, Prostaglandin / metabolism*
  • Receptors, Thromboxane / agonists
  • Receptors, Thromboxane / antagonists & inhibitors
  • Receptors, Thromboxane / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • T-Lymphocytes / metabolism*

Substances

  • Amides
  • Antihypertensive Agents
  • Receptors, Prostaglandin
  • Receptors, Thromboxane
  • prostaglandin F2alpha receptor
  • Cloprostenol
  • Bimatoprost
  • Calcium