Expression and function of A2B adenosine receptors in the U87MG tumor cells

• Published in: Drug development research 2003-04, Vol.58 (4), p.405-411
• Main Authors: Zeng, Dewan, Maa, Tenning, Wang, Uerica, Feoktistov, Igor, Biaggioni, Italo, Belardinelli, Luiz
• Format: Article
• Language: English
• Subjects: adenosine; adenosine receptors; angiogenesis; Biological and medical sciences; GPCRs; hypoxia; Medical sciences; Neuropharmacology; Neurotransmitters. Neurotransmission. Receptors; Peptidergic system (neuropeptide, opioid peptide, opiates...). Adenosinergic and purinergic systems; Pharmacology. Drug treatments
• ISSN: 0272-4391; 1098-2299
• DOI: 10.1002/ddr.10212

Adenosine is released in increased amounts during hypoxic conditions and is a potential mediator of angiogenesis. The aims of this study were to determine the effect of adenosine on the release of angiogenic factors from the glioblastoma cell line U87MG and the subtypes of adenosine receptors that mediate this effect of adenosine. The adenosine analog NECA increased the release of IL‐8 to 160±13% of control at 24 h. As a positive control, cobalt (100 µM), a metal ion capable of inducing hypoxia‐like effects, increased the release of IL‐8 to 362±99% of control at 24 h. Using real‐time RT‐PCR, it was found that U87MG cells expressed mRNA transcripts of the A1, A2A, and A2B adenosine receptors. The functional presence of A2B adenosine receptors in this cell line was confirmed using pharmacological approaches. NECA stimulated cAMP accumulations with an EC50 value of 2.93±0.91 µM and this effect of NECA was inhibited by the selective A2B antagonist IPDX. In addition, NECA also caused an increase in the intracellular calcium concentration. Furthermore, cobalt increased the level of A2B mRNA to 187±16% and 259±37% of the vehicle control at 5 h and 24 h, respectively. In conclusion, these results suggest that A2B adenosine receptors are upregulated during hypoxia and may play an important role in mediating the effect of adenosine to increase the release of angiogenic factor IL‐8 by tumor cells. Drug Dev. Res. 58:405–411, 2003. © 2003 Wiley‐Liss, Inc.