Comparison of photoaffinity labeling of P2-purinergic receptors of isolated guinea-pig vas deferens by arylazido aminopropionyl ATP and by arylazido aminobutyryl ATP.

Two chemically related arylazido photoaffinity analogs of ATP (arylazido aminopropionyl ATP (ANAPP3) and arylazido aminobutyryl ATP (ANABP3)), which have been reported in the literature to differ in their ability to inhibit myosin ATPase, were compared for their ability to antagonize contractile responses of the isolated guinea-pig vas deferens to ATP. During photolysis in organ chambers the photoconversion (delta A260/delta t) of ANAPP3 occurred with greater than first order kinetics or was multiexponential and t1/2 = 7.5 min, while delta A260/delta t for ANABP3 was first order and t1/2 = 2.25 min. After photolysis of these compounds in the presence of the guinea-pig vas deferens, using irradiation periods which caused 80% consumption of the compounds, ANABP3 was 2-3 times more potent than ANAPP3 in antagonizing contractions to ATP, which are mediated by P2-purinergic receptors. A comparison of concentration-response curves obtained for nonphotolyzed ANAPP3 and ANABP3 used as agonists suggested that the greater antagonism produced by photolyzed ANABP3 is not attributable to a greater potency. The results suggest that the longer 3'-hydroxyl-arylazide bridge length of ANABP3 places the arylnitrene intermediate in a position at or near the P2-receptor which is more favorable for covalent insertion.