Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0595921 (intraocular pressure)
 11,750 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Indoleamines are associated with circadian rhythms in pineal gland and retina. Because the ciliary epithelium has an embryonic origin similar to that of pineal gland and retina, and intraocular pressure shows circadian variations, indoleamines were searched for in aqueous humor and ciliary body in humans. In aqueous humor, serotonin, 6-hydroxymelatonin, and melatonin were simultaneously detected and measured using high-performance liquid chromatography with electrochemical detection. The concentration was 48.7 +/- 10.9 ng/ml for serotonin, 0.47 +/- 0.8 ng/ml for melatonin, and 13.9 +/- 7.7 ng/ml for 6 hydroxymelatonin. In ciliary bodies from freshly enucleated human eyes, tryptophan, 5-hydroxytryptophan, serotonin, and 5-hydroxyindoleacetic acid were detected using high-performance liquid chromatography with simultaneous fluorescence- and electrochemical detection. Finally, the enzymatic activities of arylalkylamine N-acetyltransferase (NAT) and hydroxyindole-O-methyltransferase (HIOMT), enzymes indispensable in the synthesis of melatonin, were measured. The NAT activity was 273 +/- 25 pmol/mg protein/hour and that of HIOMT, 13520 +/- 50 pmol/mg protein/hour in ciliary body. Comparison of these activities (NAT versus HIOMT) permits the suggestion that NAT is a limiting enzyme in serotonin metabolism in this tissue. These findings indicate that a circadian rhythm of indoleamines exists in human aqueous humor and that the human ciliary body is the third organ, after the pineal gland and the retina, found to synthesize indoleamines in humans.
 ...
PMID:The ciliary body--the third organ found to synthesize indoleamines in humans. 137 62

The activity of arylamine acetyltransferase with p-aminobenzoic acid (PABA), sulfamethazine (SMZ), and aminozolamide as substrates was studied in rabbit tissue homogenates of the corneal epithelium, stroma-endothelium, iris-ciliary process, and liver. Rabbits were classified as rapid or slow acetylators with respect to their rate of hepatic acetylation of SMZ. The ocular disposition of aminozolamide in the two phenotypes was compared using a topical ocular infusion method that permitted a constant concentration to remain in contact with the intact cornea. The effect of hepatic-acetylator phenotype on the intraocular pressure (IOP) recovery rate and drug concentrations in tissues after single-dose administration of aminozolamide also was studied. In general, the rank order of arylamine acetyltransferase activity regardless of substrate was liver greater than iris-ciliary process greater than corneal epithelium greater than stroma-endothelium. The specific activity with aminozolamide as substrate was greater than that with SMZ in each tissue homogenate and greater than with PABA as substrate in all tissues except the stroma-endothelium of slow hepatic-acetylator rabbits. Very low enzyme activity ratios for ocular acetylation between rapid and slow hepatic-acetylating rabbits indicated that acetylation in the ocular tissues did not correspond with the acetylation phenotype. At various times during and after topical infusion to the anesthetized rabbit, assay determinations of drug and metabolite in ocular tissues indicated that there were no significant differences between phenotypes in the disposition of either drug or metabolite. These results correlate with the IOP measurements after topical infusion; they also showed no difference in the effect of aminozolamide between hepatic-acetylator phenotypes. These results indicate that the ocular disposition and the decrease in IOP from topical application of aminozolamide is independent of the hepatic-acetylation phenotype in the rabbit. There are significant amounts of acetyltransferase activity in the ocular tissues of the rabbit with these three substrates, indicating that acetylation may be occurring for other arylamine drugs used in the eye.
 ...
PMID:Characterization of arylamine acetyltransferase in the rabbit eye. 207 33

There is evidence supporting a role for melatonin as an endogenous agent regulating intraocular pressure, but little is known about whether ocular levels of melatonin are regulated by the sympathetic nervous system, as they are in the rat pineal gland. The effects of topically applied L-timolol, norepinephrine, forskolin, domperidone and pilocarpine on levels of melatonin in regions of rabbit and chicken eyes were determined. None of these drugs altered levels of melatonin in the rabbit iris-ciliary body or in the chicken iris or ciliary body, suggesting that the actions of these drugs were not mediated through an action on melatonin. Topical forskolin did not alter N-acetyltransferase activities in rabbit iris-ciliary body. Chemical sympathectomy with 6-hydroxydopamine had no effect on nighttime levels of melatonin in rabbit iris-ciliary body or on daytime levels in chicken eyes. These results suggest that melatonin in the eyes does not appear to be under the solitary control of the adrenergic sympathetic nervous system. The data suggested a transmitter other than norepinephrine regulates N-acetyltransferase activities and melatonin levels.
 ...
PMID:Is ocular melatonin regulated by the adrenergic system? 365 29

The possible involvement of a melatonergic mechanism in the control of intraocular pressure (IOP) and the genesis of light-induced avian glaucoma (LIAG) was studied by measuring N-acetyltransferase (NAT) activity and melatonin levels in the iris, ciliary body and retina-choroid during the course of LIAG development, and in normal subjects by day and night. NAT activity was found to be significantly higher than normal in preglaucomatous and glaucomatous chicken eyes at 8, 16, and 24 weeks of age. The increase in NAT activity corresponded well with the decrease in aqueous outflow facility and preceded the development of elevated IOP by 5-6 weeks. Melatonin levels in iris and ciliary body of normal chickens and rabbits were elevated by night relative to day, which corresponded to the diurnal change in IOP. The melatonin levels in glaucomatous chicken iris and ciliary body at 24 weeks were significantly elevated relative to controls. The results suggest that melatonergic mechanisms could be involved in the elevation of IOP in LIAG. No statistical differences in choline acetyltransferase activity, adrenergic transmitter levels or dopamine concentrations could be found in tissues of LIAG eyes vs control eyes, indicating that cholinergic, adrenergic and dopaminergic mechanisms are probably not involved in LIAG.
 ...
PMID:N-acetyltransferase activity and melatonin level in the eyes of glaucomatous chickens. 388 72

Endogenous biochemical regulation of diurnal changes in intraocular pressure was investigated in rabbits. Various biochemical parameters in eye tissues, particularly the iris and ciliary body, were studied at peak (21:00 hr) and trough (09:00 hr) points of IOP. No statistical difference in choline acetyltransferase activity, adrenergic transmitter levels and dopamine concentration could be detected at these points. On the other hand, serotonin N-acetyltransferase activity was significantly higher at 21:00 hr (2.84 +/- 0.14 nmoles/mg protein/hr) than at 09:00 hr (2.18 +/- 0.16 nmoles/mg protein/hr) indicating that melatonin might be involved in the diurnal changes in IOP. Intracameral injections of various agents into rabbit eyes revealed that melatonin but not serotonin nor N-acetylserotonin raised IOP markedly, indicating that melatonin but not its precursors is involved in IOP regulation. Topical application of melatonin did not affect the IOP presumably because it does not cross the cornea effectively.
 ...
PMID:Melatonergic involvement in diurnal changes of intraocular pressure in rabbit eyes. 406 75