The phospholipase C activating P2U purinoceptor also inhibits cyclicAMP formation in DDT1 MF-2 smooth muscle cells.
The P2U purinoceptor mediated effect on cellular cAMP was investigated in DDT1 MF-2 smooth muscle cells. Stimulation of these receptors by ATP or UTP caused a pronounced decrease of about 50% in cellular cAMP levels in forskolin or isoprenaline pretreated cells. This action of the nucleotides was concentration dependent with an IC50 of 9.4 +/- 0.2 microM and 29.0 +/- 0.5 microM for UTP and ATP, respectively and was inhibited by the P2-purinoceptor antagonist suramin. The cAMP level appeared to be modified by intracellular Ca2+, represented by an initial decline in cAMP. Neither inactivation of protein kinase C by staurosporine nor elevated cytoplasmic Ca2+ concentrations interfered with the sustained decrease in cAMP levels induced by ATP or UTP, showing that this effect is not mediated via the phospholipase C pathway known to be activated after P2U purinoceptor stimulation in DDT1 MF-2 cells. Pertussis toxin inhibited the action of these nucleotides on the cellular cAMP level. It can be concluded that the P2U purinoceptor in DDT1 MF-2 cells is coupled to different G-proteins, activating phospholipase C and inhibiting adenylyl cyclase activity.
Sipma
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H
Groningen Institute for Drugs Studies (GIDS), Department of Pharmacology/Clinical Pharmacology, University of Groningen, Netherlands.
den Hertog
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Nelemans
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D000255:Adenosine Triphosphate / Q000494:pharmacology; D037361:Adenylate Cyclase Toxin; D000818:Animals; D002460:Cell Line; D005576:Colforsin / Q000494:pharmacology; D006224:Cricetinae; D000242:Cyclic AMP / Q000096:biosynthesis*; D004789:Enzyme Activation / Q000187:drug effects; D019204:GTP-Binding Proteins / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism*; D037342:Pertussis Toxin; D018048:Receptors, Purinergic P2 / Q000502:physiology*; D010738:Type C Phospholipases / Q000378:metabolism*; D014544:Uridine Triphosphate / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D037361:Adenylate Cyclase Toxin; D018048:Receptors, Purinergic P2; D010566:Virulence Factors, Bordetella; D005576:Colforsin; D000255:Adenosine Triphosphate; D000242:Cyclic AMP; D037342:Pertussis Toxin; D010738:Type C Phospholipases; D019204:GTP-Binding Proteins; D007545:Isoproterenol; D014544:Uridine Triphosphate