Strial prostaglandins and leukotrienes. Biochemical characteristics and interrelationship with furosemide

Synthesis of prostaglandins (PGs) was characterized in the lateral wall (LW) of guinea-pig cochlea. Basal synthesis at 37 degrees C was about 480 pg/LW (12.8 ng X mg-1 protein) for PGI2 and 85 pg/LW (2.3 ng X mg-1 protein) for PGE2, levelling out after 10 min of incubation. Incubation with arachidonic acid (10(-5) M) increased PGI2 and PGE2 synthesis by 44% and 1020%, respectively, showing that arachidonic acid availability is a synthesis-limiting factor. The stimulating effect of the Ca++ ionophore A23187 (5 X 10(-6) M) on PG synthesis was weak (about +50%) but was enhanced (about +140%) by preincubation with arachidonic acid. Angiotensin II (10(-6) M), vasopressin (5 X 10(-7) M), and furosemide (10(-8) to 10(-3) M) did not alter PG secretion. Neither aspirin nor indomethacin prevented the development of furosemide ototoxicity (endocochlear potential) in the rat. Perfusion with PGI2 influenced the furosemide effect in some instances.