[Presynaptic 5-hydroxytryptamine receptors enhance cholinergic neurosecretion in the human iris-ciliary body].
OBJECTIVE
To characterize presynaptic 5-hydroxytryptamine (5-HT) heteroreceptors which modulate 3H-acetylcholine (3H-ACh) release in isolated human iris-ciliary bodies (ICBs).


METHODS
ICB tissue segments were perfused and incubated with 3H-choline, and electrically stimulated four times (S1, S2, S3 and S4) at 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 were determined by the stimulation ratio (Sx/S1) of evoked 3H-ACh release. 3H-ACh in perfusate fractions was isolated by ion exchange chromatography and analyzed for radioactivity by liquid scintillation spectrometry.


RESULTS
The evoked 3H-ACh release was enhanced in a concentration-dependent manner by 5-HT [10(-9)-10(-5) mol/L, 50% effective concentration values (EC50) = 3.36 x 10(-8) mol/L] as well as 5-methoaxytryptamine [5-MOT (agonist), 10(-8)-10(-5) mol/L, EC50 = 6.59 x 10(-7) mol/L]. The selective 5-HT4 antagonist, GR113808A (10(-8) mol/L) inhibited the 5-HT-inducing increase of the cholinergic response, producing parallel right shifts of the 5-HT concentration-response curves (t = 4.012, P < 0.01). The selective 5-HT3 antagonist ondersetron (5 x 10(-7) mol/L) and tropisetron (10(-9) mol/L) did not affect 5-HT inducing 3H-Ach release (t = 2.215, P > 0.05).


CONCLUSIONS
Our results indicate that cholinergic terminals in the human ICB contain 5-HT heteroreceptors that may promote the release of 5-HT and belong to the 5-HT4 subtype.
Yang
X
X
Department of Ophthalmology, Tang-Du Hospital, Fourth Military Medical University, Xi'an, 710038, China.
Jumblatt
J E
JE
D008735:5-Methoxytryptamine / Q000494:pharmacology; D000109:Acetylcholine / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002924:Ciliary Body / Q000187:drug effects / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D007498:Iris / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D017294:Ondansetron / Q000494:pharmacology; D017661:Receptors, Presynaptic / Q000502:physiology*; D011985:Receptors, Serotonin / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D014316:Tritium; D000077526:Tropisetron
D007211:Indoles; D017661:Receptors, Presynaptic; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D014316:Tritium; D012701:Serotonin; D008735:5-Methoxytryptamine; D017294:Ondansetron; D000077526:Tropisetron; D000109:Acetylcholine