Adenosine receptor activation and the regulation of tyrosine hydroxylase activity in PC12 and PC18 cells.
We compared the response of rat PC12 cells and a derivative PC18 cell line to the effects of adenosine receptor agonists, antagonists, and adenine nucleotide metabolizing enzymes. We found that theophylline (an adenosine receptor antagonist), adenosine deaminase, and AMP deaminase all decreased basal cyclic AMP content and tyrosine hydroxylase activity in the PC12 cells, but not in PC18 cells. Both cell lines responded to the addition of 2-chloroadenosine and 5'-N-ethylcarboxamidoadenosine, adenosine receptor agonists, by exhibiting an increase in tyrosine hydroxylase activity and cyclic AMP content. The latter finding indicates that both cell lines contained an adenosine receptor linked to adenylate cyclase. We found that the addition of dipyridamole, an inhibitor of adenosine uptake, produced an elevation of cyclic AMP and tyrosine hydroxylase activity in both cell lines. Deoxycoformycin, an inhibitor of adenosine deaminase, failed to alter the levels of cyclic AMP or tyrosine hydroxylase activity. This suggests that uptake was the primary inactivating mechanism of adenosine action in these cells. We conclude that both cell types generated adenine nucleotides which activate the adenosine receptor in an autocrine or paracrine fashion. We found that PC12 cells released ATP in a calcium-dependent process in response to activation of the nicotinic receptor. We also measured the rates of degradation of exogenous ATP, ADP, and AMP by PC12 cells. We found that the rates of metabolism of the former two were at least an order of magnitude greater than that of AMP. Any released ATP would be rapidly metabolized to AMP and then more slowly degraded to adenosine.(ABSTRACT TRUNCATED AT 250 WORDS)
Roskoski
R
R
Department of Biochemistry and Molecular Biology, Louisiana State University Medical Center, New Orleans 70119.
Roskoski
L M
LM
D000227:Adenine Nucleotides / Q000494:pharmacology; D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology*; D000243:Adenosine Deaminase / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000378:metabolism; D000310:Adrenal Gland Neoplasms; D000818:Animals; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D004176:Dipyridamole / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology; D007700:Kinetics; D015649:Pentostatin / Q000494:pharmacology; D010673:Pheochromocytoma; D051381:Rats; D011983:Receptors, Purinergic / Q000187:drug effects / Q000502:physiology*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*
D000227:Adenine Nucleotides; D011983:Receptors, Purinergic; D015649:Pentostatin; D000431:Ethanol; D004176:Dipyridamole; D000255:Adenosine Triphosphate; D000242:Cyclic AMP; D014446:Tyrosine 3-Monooxygenase; D000243:Adenosine Deaminase; D000241:Adenosine