UTP activates phospholipase C-Ca2+ system through a receptor different from the 53-kDa ATP receptor in PC12 cells.
Extracellular ATP (a purine nucleotide) and UTP (a pyrimidine nucleotide) both activated phospholipase C with a similar potency and efficacy; however, in contrast to ATP which induced a remarkable norepinephrine release, UTP-induced norepinephrine release was small in PC12 cells, a rat pheochromocytoma cell line. ATP, its derivatives (2-methylthioadenosine 5'-triphosphate (MeSATP) and 2'- and 3'-O-(4-benzoylbenzoyl)adenosine 5'-triphosphate (BzATP)) and UTP increased intracellular Ca2+ in the presence of 2 mM extracellular Ca2+ with the potency order of ATP > MeSATP > BzATP = UTP. Under the low extracellular Ca2+ conditions, the Ca2+ response to purine nucleotides was markedly reduced, but the UTP response was not. The [32P]BzATP labeling of a 53-kDa putative ATP receptor coupled to a channel system (Majid, M.A., Okajima, F., and Kondo, Y. (1992) Biochim. Biophys. Acta 1136, 283-289) was markedly inhibited by ATP, but not by UTP. These results suggest that UTP activates the phospholipase C-Ca2+ system through a receptor different from the 53-kDa ATP receptor.
Majid
M A
MA
Department of Physical Biochemistry, Gunma University, Maebashi, Japan.
Okajima
F
F
Kondo
Y
Y
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology*; D000345:Affinity Labels / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D007295:Inositol Phosphates / Q000378:metabolism*; D007700:Kinetics; D008970:Molecular Weight; D009638:Norepinephrine / Q000378:metabolism*; D016716:PC12 Cells; D011983:Receptors, Purinergic / Q000187:drug effects / Q000378:metabolism*; D010738:Type C Phospholipases / Q000378:metabolism*; D014544:Uridine Triphosphate / Q000494:pharmacology*
D000345:Affinity Labels; D007295:Inositol Phosphates; D011983:Receptors, Purinergic; C033901:3'-O-(4-benzoyl)benzoyladenosine 5'-triphosphate; D000255:Adenosine Triphosphate; D010738:Type C Phospholipases; D002118:Calcium; D014544:Uridine Triphosphate; D009638:Norepinephrine