RELEASE OF H-3 5-HYDROXYTRYPTAMINE FROM ISOLATED RABBIT AORTA

The main aim of the present investigation was to study systematically the passive and stimulation-evoked release of H-3-5-hydroxytryptamine (H-3-5-HT) from rabbit isolated aorta. This was accomplished by preloa ding rings of aorta with H-3-5-HT (10(-6)M) and then monitoring by fra ctional collection the basal H-3-outflow and stimulation-evoked H-3-ov erflow. The basal H-3-outflow from aorta preloaded with 10(-6)M of eit her H-3-5-HT or (-)-H-3-noradrenaline (H-3-NA) leveled off about 100 m in. after the onset of wash-out and remained almost constant thereafte r (100-240 min.). The basal H-3-outflow from tissue preloaded with H-3 -5-HT was almost 3-fold higher (70-240 min.) than that seen after prel oading with H-3-NA. Cocaine (3X10(-5)M) did not alter the basal H-3-ou tflow (15-240 min.) from tissue preloaded with H-3 5-HT, while pargyli ne (5X10(-4)M) decreased it by about 66% (100-240 min.). Electrical-fi eld stimulation (S-1-S-7, 200 mA, 600 pulses, 0.5 msec., 3 Hz) were ap plied to the tissue. The initial stimulation-evoked H-3-overflow from aorta preloaded with H-3-5-HT was higher than the subsequent ones (S-1 -S-7: 100, 35, 35, 35, 35, 37, and 40%). Similar results to these were obtained with tissues preloaded with H-3-NA. The stimulation (S-1-S-7 ; 200 mA; 600 pulses, 0.5 msec, 3 Hz)-evoked H-3-overflow increased in an apparent linear manner with the amount of current used (50-200 mA) . This was also the case for number of pulses (100-900) in the stimulu s. The stimulation-evoked H-3-overflow depended in part on the stimula tion frequency: unchanged at 2-4 Hz; small increase at 8 Hz; and a 15- fold increase at 16 Hz relative to 2 Hz. Tetrodotoxin (10(-6)M) decrea sed the stimulation-evoked H-3-overflow from aorta preloaded with H-3- 5-HT (S-2-S-6) by about 60%, while S-1 was not affected. The inhibitor y effect of tetrodotoxin was fully reversed by washing the aorta with drug-free salt solution. Omission of Ca2+ from the salt solution reduc ed the stimulation H-3-overflow by 47-57% (S-2-S-6) while S-1 was unaf fected. 6-Hydroxydopamine markedly increased the stimulation-evoked H- 3-overflow from H-3-5-HT preloaded rings (180-323% of control). Pargyl ine (5X10(-4)M), cocaine (3X10(-5)M) and removal of endothelium did no t alter the stimulation-evoked H-3-overflow evoked by stimulation (S-1 -S-6) of aorta preloaded with H-3-5-HT. It is concluded that H-3-5-HT can be released by electrical-field stimulation as a ''false transmitt er'' from rabbit isolated aorta. Most of the release is probably of ne uronal origin. However, some of the stimulation-evoked H-3-overflow is derived from extraneuronal sites.