DIFFERENTIAL INHIBITORY POTENCIES OF NONSTEROIDAL ANTIINFLAMMATORY DRUGS ON SMOOTH-MUSCLE PROSTANOID SYNTHESIS

In isolated rat aorta and urinary bladder, indomethacin inhibited the synthesis of the prostaglandins (PG) PGI2, PGE2, PGF2α and TXA2 equipotently when PG synthesis was stimulated with excitatory receptor agonists (noradrenaline and carbochol), fluoride (a G protein activator), phorbol ester (a protein kinase C (PKC) activator) and calcium ionophore A23187 (a creator of artificial calcium channels). However, there was a marked right shift (30 fold) in the indomethacin concentration-inhibition curves when PG synthesis was stimulated by arachidonate (PG substrate) and trauma (freeze fracturing and sonication). Although less potent than indomethacin, the NSAIDs tiaprofenic acid and ibuprofen showed a similar disparity between the IC50s with the same PG stimulators. Since PG synthesis stimulated by receptor agonists, fluoride, phorbol ester and A23187 is dependent on calcium channel activation whereas trauma and arachidonate-stimulated PG synthesis bypass calcium channel activation, these data indicate that NSAIDs inhibit not only cyclooxygenase but also (and more potently) the mobilisation of Ca2+ linked to PG synthesis in these tissues. © 1990.