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Adenosine inhibits cell division and promotes neurite extension in PC12 cells
Author(s) -
Huffaker Tom,
Corcoran Teresa,
Wagner John A.
Publication year - 1984
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.1041200212
Subject(s) - adenosine , adenosine kinase , adenosine receptor , adenosine a1 receptor , adenosine a2b receptor , adenosine deaminase , neurite , purinergic signalling , biology , adenosine a3 receptor , adenosine deaminase inhibitor , ehna , inosine , microbiology and biotechnology , agonist , medicine , endocrinology , biochemistry , chemistry , receptor , in vitro
Low concentrations (10–50 μM) of adenosine (EC 50 = 17 μM) or chloroadenosine (EC 50 = 23 μM) prevent the division of PC12 cells. This inhibition is not mimicked by guanosine, inosine, 3′,5′ dideoxyadenosine, phenylisopropylad‐enosine, or adenylylimidodiphosphate. The growth inhibition is not relieved by addition of uridine or deoxycytidine, nor is it potentiated by homocysteine thiolactone. Inhibition of adenosine uptake does not inhibit adenosine‐de‐pendent growth arrest. PC12 variants that are deficient in adenosine kinase are as sensitive as wild‐type cells to the growth‐inhibitory effects of adenosine. These experiments suggest that adenosine prevents cell division at an adenosine receptor rather than acting after being metabolically altered. The adenosine receptor that inhibits cell division does not appear to be the adenosine receptor that stimulates adenylate cyclase for these reasons: (1) phenylisopropyladenosine, which is a potent agonist of this receptor, does not inhibit cell division; (2) 3′,5′ dideoxyadenosine does not antagonize the effect of adenosine on cell division; and (3) theophylline does not affect growth inhibition by adenosine. Thus, these experiments suggest the existence of a second adenosine receptor that can inhibit cell division. Adenosine also promotes the morphological differentiation of PC12 cells. In the presence of the adenosine deaminase inhibitor, erythro‐9‐(2‐hydroxy‐3‐nonyl)adenosine (EHNA), adencsine causes the formation of short neurites (one‐half to one and one‐half cell diameters in length). Adenosine also increases the rate of neurite formation of both long and short neurites in response to NGF.