Purpose: To characterize prejunctional 5-HT heteroreceptors which modulate nacetylcholine (3 H-ACh release) in isolated rabbit and human iris-ciliary bodies (ICBS) . Methods: ICB tissue segments were incubated with H-choline, superfused and electrically stimulated four times (S1,S2,S3,S4) at 3 - 10 Hz for 1 min to elicit 3H-ACh. secretion. Test agents (5-HT agonists and antagonists) were added before S2,S3 and S4 and their effects determined by the stimulation ratio (Sx/S1) of evoked 3H-ACh. release. 3H-ACh in super-fusate fractions was fractionated and quantified by ion exchange chromatography. Results: In rabbit ICBs, evoked 3H-ACh. release was enhanced in a concentration-dependent manner by 5-HT (10- 9 - 10-5 M, EC50 = 5.8× 10-8 M). The maximum effect of 5-HT (10-6M) corresponded to a 45. 14 ± 7.40%) (n = 6) increase in 3H-ACh release. Higher concentrations of 5-HT ( > 10- M) induced desensitization. The response to 5-HT ( 10-6 M) in the presence of the 5-HT3/4 antagonist tropisetron (10-9 M) , 5-H Purpose: To characterize prejunctional 5-HT heteroreceptors which modulate nacetylcholine (3 H-ACh release) in isolated rabbit and human iris-ciliary bodies (ICBS). Methods: ICB tissue segments were incubated with H-choline, superfused and electrically stimulated four times Test agents (5-HT agonists and antagonists) were added before S2, S3 and S4 and their effects determined by the stimulation (S1, S2, S3, S4) at 3-10 Hz for 1 min to elicit 3H- 3H-ACh in super-fusate fractions was fractionated and quantified by ion exchange chromatography. Results: In rabbit ICBs, evoked 3H-ACh. release was enhanced in a concentration-dependent (Sx / S1) of evoked 3H-ACh. The maximum effect of 5-HT (10-6M) was corresponded to a 45. 14 ± 7.40%) (n = 10-5 M, EC50 = 5.8x10-8 M) High concentrations of 5-HT (> 10-M) induced desensitization. The response to 5-HT (10-6 M) in the presence of the 5-HT3 / 4 antagonist tropiset ron (10-9 M), 5-H