Potentiation of retinoic acid-induced differentiation of HL-60 cells by prostaglandin EP2 receptor.
Human promyeloid HL-60 cells are differentiated by all-trans retinoic acid (RA) to granulocytes, and prostaglandin (PG) E2 potentiates the RA-induced differentiation. Here we examined which subtype of PGE receptors was involved in this potentiating activity of PGE2. Northern blot analysis demonstrated that HL-60 cells expressed three subtypes of PGE receptor, EP2, EP3, and EP4. Among various EP agonists, and EP2-selective agonist, butaprost, preferentially potentiated the RA-induced differentiation of HL-60 cells. Butaprost not only decreased the half-maximal concentration of RA but also increased the maximal level of the differentiation. Butaprost concentration-dependently stimulated the cAMP formation, and 8-Br-cAMP strongly potentiated the RA-induced differentiation. These results demonstrate that the EP2 receptor enhances the RA-induced differentiation of HL-60 cells via stimulation of adenylate cyclase.
Department of Physiological Chemistry, Faculty of Pharmaceutical Sciences, Kyoto University, Japan.
S
S
Ishiguro
N
N
Takahashi
K
K
Nemoto
M
M
Negishi
A
A
Ichikawa
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000527:Alprostadil / Q000031:analogs & derivatives / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects*; D000242:Cyclic AMP / Q000096:biosynthesis; D015232:Dinoprostone / Q000494:pharmacology*; D004357:Drug Synergism; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000378:metabolism; D018922:HL-60 Cells; D006801:Humans; D011459:Prostaglandins E, Synthetic; D018102:Receptors, Leukotriene B4 / Q000502:physiology; D018078:Receptors, Prostaglandin E / Q000502:physiology*; D058307:Receptors, Prostaglandin E, EP2 Subtype; D014212:Tretinoin / Q000494:pharmacology*
C545644:PTGER2 protein, human; D011459:Prostaglandins E, Synthetic; D018102:Receptors, Leukotriene B4; D018078:Receptors, Prostaglandin E; D058307:Receptors, Prostaglandin E, EP2 Subtype; D015124:8-Bromo Cyclic Adenosine Monophosphate; D014212:Tretinoin; D000242:Cyclic AMP; D019205:GTP-Binding Protein alpha Subunits, Gs; D000527:Alprostadil; C048491:butaprost; D015232:Dinoprostone