Serotonergic and endothelin (ET)-1 effects on aqueous humor dynamics in monkeys

C. Millar, J. Kiland, J. Peterson, W. C. Hubbard, N. M. Osborne, P. L. Kaufman

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Abstract

Purpose. To determine effect of 5-HT agonists and ET-1 on aqueous flow (AHF) and outflow facility (C). Methods. Living cynomolgus monkeys received, unilaterally: (1) 5-HT agonists (serotonin, 5-CT (5-HT1), sumatripan (5-HT1D), gepirone (5-HT1A), (all 1%/10%, n=8), 8-OH DPAT (5HT1A, 1%, n=4)) topically (6x5μl), with IOP (tonometry) and AHF (fluorophotometry) measured for 6h post-Rx; (2) intracameral (i.c.) ET-1 (10μl, n=4, final i.c. conc. 0.1-10nM), with C (perfusion) measured for 1h post-Rx; (3) intravitreal (i.v.) ET-1 in 0.01% acetic acid (20μl, n=4, final i.v. conc. 0.1-1μM), with AHF measured for 6h starting 12n and 24h post-Rx. Contralateral eyes received vehicle. Results. Serotonergics (except 8-OH DPAT) did not affect IOP or AHF. 8-OH DPAT caused an AHF increase of 1.06±0.23 μl/min (98.8±22.2%) (mean±s.e.m., P<0.01, 2-tailed t-test, ipsilateral & contralateral combined) over 6h, compared with 6h baseline measurements 1 week pre-Rx. IOP (determined pre-Rx and then every 30 min for 6h) dropped by 5.6±1.6 mmHg (P<0.05, ipsilateral&contralateral combined; comparing IOP pre- and 6h post-Rx). No difference between ipsilateral & contralateral AHF or IOP was seen. The IOP drop was greater than in untreated ketamine-anesthetized monkeys over the same period. ET-1 did not affect AHF or C. Conclusions. Despite reports of serotonergic IOP modulation in subprimates, ET-1 receptors in rabbit/human ciliary epithelium, and ET-1-ergic C increases in monkeys, we found limited evidence of serotonergic and no evidence of ET-1 effects on monkey aqueous dynamics. Results for 8-OH DPAT indicate a 5-HT1A or 5-HT1A-like receptor in monkey ciliary epithelium.

Original languageEnglish
Pages (from-to)S836
JournalInvestigative Ophthalmology and Visual Science
Volume37
Issue number3
StatePublished - 15 Feb 1996

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    Millar, C., Kiland, J., Peterson, J., Hubbard, W. C., Osborne, N. M., & Kaufman, P. L. (1996). Serotonergic and endothelin (ET)-1 effects on aqueous humor dynamics in monkeys. Investigative Ophthalmology and Visual Science, 37(3), S836.