The structural conformation of the polyphosphate chain of the ATP molecule is critical for its promotion of prostaglandin biosynthesis.

The adenine nucleotide ATP relaxed the tracheal strip of the guinea pig, while the methylene isosteres of ATP, alpha, beta-methylene ATP (APCPP) and beta, gamma-methylene ATP (APPCP) in concentrations up to 100 micrograms were either inactive or produced a small contraction. The relaxation of the tracheal strip elicited by ATP was completely abolished by treatment of the tissue with indomethacin, a prostaglandin synthesis inhibitor. The relaxations induced by ATP in the guinea-pig taenia coli were followed by a rebound contraction which could be blocked by indomethacin. The two methylene analogues of ATP, produced relaxations in the taenia coli which were not followed by a rebound contraction. It is concluded that in the guinea-pig tracheal chain and taenia coli preparations ATP stimulated prostaglandin synthesis while the analogues modified in the polyphosphate chain were unable to do so.