Effect of arylazido aminopropionyl ATP (ANAPP3), on ATP responses of isolated guinea pig smooth muscle.

Arylazido aminopropionyl ATP (ANAPP3), a photoaffinity analogue of adenosine 5'-triphosphate, photoactivated with visible light (+hv), specifically and irreversibly antagonized ATP contractions of the guinea pig vas deferens. ANAPP3 (30 microM) antagonized responses to exogenously added ATP in untreated, and in tissues pretreated with indomethacin (2.9 microM) and 6-(2-hydroxy-5-nitrobenzyl)-thio guanosine (10 microM). It was of interest to see if this pharmacological antagonist of ATP could be used to assess the validity of the purinergic nerve hypothesis by allowing a differentiation between, or proof of the identity of, responses to ATP and the non-adrenergic inhibitory transmitter in guinea pig stomach fundus. After photoactivation (+hv) in the organ bath and subsequent washout, ANAPP3 (30 and 100 microM) failed to antagonize relaxant responses to ATP (1.0 - 1000 microM) in fundic strips. In addition ANAPP3 failed to antagonize ATP-induced inhibition of the twitch response in electrically stimulated guinea pig ileum longitudinal muscle strips. We conclude that ANAPP3 does not antagonize all actions of ATP, which may limit its usefulness in assessing the above hypothesis. Results with this compound suggest that ATP excitatory receptors may differ from those mediating relaxation and other ATP actions.