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Biotech / Medical : Neuroscience

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To: Marty who wrote (119)	10/29/2000 10:13:27 PM
From: Nikole Wollerstein	of 278

I think the in paper Nature 12 October 2000 shed some light on the mechanism of Neotrofin action. nature.com Unfortunately you should have paid subscription to Nature to read the paper on line "Netrin-1-mediated axon outgrowth and cAMP production requires interaction with adenosine A2b receptor" The netrins, a family of laminin-related secreted proteins, are critical in controlling axon elongation and pathfinding1-4. The DCC (for deleted in colorectal cancer) protein was proposed as a receptor for netrin-1 in the light of many observations including the inhibition of netrin-1-mediated axon outgrowth and attraction in the presence of an anti-DCC antiserum5-7, the similitude of nervous system defects in DCC and netrin-1 knockout mice4, 8 and the results of receptor swapping experiments9. Previous studies have failed to show a direct interaction of DCC with netrin-1 (ref. 10), suggesting the possibility of an additional receptor or co-receptor. Here we show that DCC interacts with the membrane-associated adenosine A2b receptor, a G-protein-coupled receptor that induces cAMP accumulation on binding adenosine11. We show that A2b is actually a netrin-1 receptor and induces cAMP accumulation on binding netrin-1. Finally, we show that netrin-1-dependent outgrowth of dorsal spinal cord axons directly involves A2b. Together our results indicate that the growth-promoting function of netrin-1 may require a receptor complex containing DCC and A2b. Here is conclusion : The implication of the A2b receptor in mediating netrin-1-dependent axon outgrowth indicates that adenosine receptors may have a function in the nervous system, far away from their known activity in neurotransmission. Here is conclusion: The implication of the A2b receptor in mediating netrin-1-dependent axon outgrowth indicates that adenosine receptors may have a function in the nervous system, far away from their known activity in neurotransmission. My comments: AIT-082 have adenosine backbone and I can speculate that it can bind to the same receptor as adenosine and co activate netrin-1 receptor

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