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Biotech / Medical : CVTX - CV Therapeutics, Inc. -- Ignore unavailable to you. Want to Upgrade?

To: scaram(o)uche who wrote (136)	12/9/2003 2:56:24 PM
From: scaram(o)uche	Read Replies (1) \| Respond to of 411

Lange recently said that they were going to stick with cardiovascular, despite the potential application of AR antagonists and agonists to a wide variety of diseases (and large markets). Nonetheless, sure seems like they're competitive, knowledge-wise, in asthma?? I have wondered if they have any good non-CV stuff to out-license. Again, I don't know the company particularly well....... Am J Respir Cell Mol Biol. 2003 Jul 10 [Epub ahead of print]. A2B Adenosine Receptors Increase Cytokine Release by Bronchial Smooth Muscle Cells. Zhong H, Belardinelli L, Maa T, Feoktistov I, Biaggioni I, Zeng D. Department of Drug Research and Pharmacological Sciences, CV Therapeutics, Inc., Palo Alto, CA, USA. Adenosine (Ado) has been suggested to play a role in inflammatory airway diseases such as asthma and COPD. The goal of this study was to determine the effect of Ado and its receptor subtypes on cytokine release by BSMCs. The A2B AdoR was expressed at the highest level among the four AdoR subtypes. Activation of the A2B AdoR by an Ado analog, NECA, increased cAMP accumulation with potency (EC50 value) of 21.2+/-0.2 micro M. The effect of NECA on the expression of the inflammatory cytokines was determined using a complementary DNA (cDNA) array consisting of 23 cytokine genes and confirmed using real-time RT-PCR and ELISA. NECA increased the release of IL-6 and MCP-1 proteins with EC50 values of 1.26+/-0.25 micro M and 0.40+/-0.08 micro M, respectively, and the maximal folds of induction were 20.8+/-1.7 and 6.4+/-0.7 fold, respectively. Selective agonists for the A1, A2A, and A3 AdoR subtypes had no effect on cytokine release. The effects of NECA were attenuated by selective antagonists of the A2B AdoR. Thus, Ado increases the release of IL-6 and MCP-1 from BSMCs via activation of the A2B AdoR. Our findings provide a novel mechanism whereby adenosine acts as a proinflammatory mediator in the airway.