Pyrimidine nucleotide-evoked inhibition of cyclic amp accumulation in equine epithelial cells

Uridine triphosphate (UTP) evoked inhibition of adrenaline-evoked cAMP accu mulation in cultured equine epithelial cells (EC50, 1.8 +/- 0.2 mu M) and t his effect was mimicked by 5-Br-UTP (EC50, 6.6 +/- 1.8 mu M) and uridine di phosphate (UDP; EC50, 96 +/- 26 mu M). This inhibitory action of UTP was ab olished by pre-treating cells with pertussis toxin (10 ng ml(-1), 24 h). UT P (EC50, 2.3 +/- 0.3 mu M) and 5-Br-UTP (EC50, 29.4 +/- 9.4 mu M) also incr eased intracellular free calcium ([Ca2+](i)) whilst UDP did not; the two ef fects are thus differentially sensitive to these pyrimidine nucleotides. AT P evoked cAMP accumulation in control cells and this response was unaffecte d by pertussis toxin. There is, therefore, no indication that ATP activates the pertussis toxin-sensitive inhibitory pathway. The UTP-evoked inhibitio n of cAMP accumulation was abolished by isobutylmethylxanthine (IBMX, 5 mM) and so the negative control over cAMP levels appears to be mediated by rec eptors that are selectively activated by pyrirmidine nucleotides and permit control over phosphodiesterase activity.