Pyrimidine nucleotide-evoked inhibition of cyclic AMP accumulation in equine epithelial cells.
Uridine triphosphate (UTP) evoked inhibition of adrenaline-evoked cAMP accumulation in cultured equine epithelial cells (EC50, 1.8 +/- 0.2 microM) and this effect was mimicked by 5-Br-UTP (EC50, 6.6 +/- 1.8 microM) and uridine diphosphate (UDP; EC50, 96 +/- 26 microM). This inhibitory action of UTP was abolished by pre-treating cells with pertussis toxin (10 ng ml-1, 24 h). UTP (EC50, 2.3 +/- 0.3 microM) and 5-Br-UTP (EC50, 29.4 +/- 9.4 microM) also increased intracellular free calcium ([Ca2+]i) whilst UDP did not; the two effects are thus differentially sensitive to these pyrimidine nucleotides. ATP evoked cAMP accumulation in control cells and this response was unaffected by pertussis toxin. There is, therefore, no indication that ATP activates the pertussis toxin-sensitive inhibitory pathway. The UTP-evoked inhibition of cAMP accumulation was abolished by isobutylmethylxanthine (IBMX, 5 mM) and so the negative control over cAMP levels appears to be mediated by receptors that are selectively activated by pyrimidine nucleotides and permit control over phosphodiesterase activity.
Wilson
S M
SM
Division of Neuroscience and Biomedical Systems, University of Glasgow, UK. s.m.wilson@dundee.ac.uk
Gallagher
M
M
Rakhit
S
S
Remsbury
A L
AL
Ko
W H
WH
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002461:Cell Line, Transformed; D000242:Cyclic AMP / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004791:Enzyme Inhibitors; D004837:Epinephrine / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D006736:Horses; D037342:Pertussis Toxin; D018048:Receptors, Purinergic P2 / Q000187:drug effects / Q000378:metabolism; D013545:Sweat Glands / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D019284:Thapsigargin / Q000494:pharmacology; D014500:Uracil Nucleotides / Q000494:pharmacology*; D014530:Uridine Diphosphate / Q000494:pharmacology; D014544:Uridine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D004791:Enzyme Inhibitors; D018048:Receptors, Purinergic P2; D014500:Uracil Nucleotides; D010566:Virulence Factors, Bordetella; C018009:5-bromouridine triphosphate; D014530:Uridine Diphosphate; D019284:Thapsigargin; D000255:Adenosine Triphosphate; D000242:Cyclic AMP; D037342:Pertussis Toxin; D002118:Calcium; D015056:1-Methyl-3-isobutylxanthine; D014544:Uridine Triphosphate; D004837:Epinephrine