PREJUNCTIONAL MODULATION BY PROSTAGLANDIN E(2) OF NORADRENALINE RELEASE FROM SYMPATHETIC NEURONS IN RABBIT AORTA

The modulating effect of prostaglandin E(2) (PGE(2)) on the electrical ly-evoked H-3-overflow from rabbit isolated aorta preloaded with H-3-n oradrenaline was examined. PGE(2) (3x10(-9)-3x10(-7) M) inhibited the stimulation-evoked H-3-overflow (maximum inhibition: 81%; pIC(50): 8.1 ). The inhibition was reversible and inversely related to stimulation frequency (1-30 Hz). Cocaine (3x10(-5)M) and corticosterone (4x10(-5)M ) did not alter the inhibitory effect of PGE(2) (3x10(-9)-10(-7)M). Ra uwolscine (10(-6)M) enhanced the reduction caused by PGE(2) (3x10(-9)- 10(-7)M). Rauwolscine (10(-6)M) alone enhanced the H-3-overflow by 360 %. Indomethacin (3x10(-6)M) and suprofen (4x10(-5)M) did not alter the PGE(2) (3x10(-9)-10(-7)M)-induced reduction of the H-3-overflow. Indo methacin (3x10(-6)M) and suprofen (4x10-(5)M) alone had no effect. We conclude that in the rabbit aorta (1) PGE(2) modulates noradrenaline r elease from sympathetic neurones through a prejunctional inhibitory re ceptor mechanism; (2) that there is an interaction between alpha(2)-ad renoceptors and EP-receptors; (3) that uptake inhibition does not affe ct the effect of PGE(2); and (4) that the influence of endogenous pros taglandins on the noradrenaline release can be excluded.