The effects of forskolin on cyclic AMP, intraocular pressure and aqueous humor formation in rabbits

Bartels, S P; Lee, Susan R.; Neufeld, Arthur H.

doi:10.3109/02713688709025183

Cited by 25 publications

(6 citation statements)

References 19 publications

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“…The authors also recorded no changes in blood pressure and pulse during and after topical ocular delivery of forskolin in rabbits and humans, and observed no tolerance to the intraocular pressure lowering effect in rabbits after topical doses given every 6 h for 15 days. In addition, forskolin was found to stimulate cAMP production in rabbit cultured corneal epithelial cells, increase cAMP concentration in the aqueous humor 10fold and cause a prolonged reduction of intraocular pressure and a decrease in aqueous humor formation [115]. It has however been shown that topical application of 1% forskolin did not significantly decrease the intraocular pressure in glaucomatous monkey eyes after the second day of the treatment [116].…”

Section: Forskolinmentioning

confidence: 99%

Plectranthus barbatus: A Review of Phytochemistry, Ethnobotanical Uses and Pharmacology – Part 2

Alasbahi

Melzig²

2010

Planta Med

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Pharmacology ! Plectranthus barbatusStudies on several extracts with various polarities obtained from different parts of P. barbatus revealed a number of pharmacological properties that may justify most of the traditional uses of P. barbatus, for example, organic extracts were reported to possess anti-inflammatory, antimicrobial [1, 2], antioxidant [3], cytotoxic [4], hypotensive [5,6], spasmolytic [7], hepatoprotective [8] and antifeedant [9] activities as well as activity against Ehrlichʼs ascites tumor in mice [10]. An alcoholic extract of the P. barbatus roots was shown to exhibit marked inhibitory action against Escherichia coli toxin-induced secretory response in rabbits and guinea pig ileal loops [11]. It has been shown that a hydroalcoholic extract of P. barbatus (880 mg/kg/day) exerted a variety of toxic effects on the different periods of pregnancy in rats; for example, in the period before embryo implantation, it caused a delay in fetal development and anti-implantation and, after embryo implantation, a delay in the development associated with maternal toxicity [12]. The water extract of P. barbatus leaves was found to exert hypoglycemic, hypotensive and antispasmodic activities [13]. It has been demonstrated that the water extract (WE) of the stems and leaves, at a dose of 1 g/kg p. o., shortened the sleeping time induced by pentobarbital by 37 %, and at a dose of 2 g/kg p. o. enhanced the intestinal transit of charcoal by 30% in mice. The WE (2 g/kg/intraduodenal) also reduced the gastric secretions (3.9 ± 1.0 to 0.5 ± 0.2 mL/4 h), and total acid secretion (34.4 ± 11.0 to 2.7 ± 0.5 mEq/L) and raised gastric pH (2.2 ± 0.3 to 6.5 ± 0.8) in rats. The treatment with WE (2 g/ kg p. o.) was also found to protect against lesions induced by ethanol or cold-restraint stress, in pylorus-ligated rats [14]. Similar results were obtained by Schultz et al. [15] who reported that the WE of the leaves (0.5-0.1 g/kg) injected into the duodenal lumen decreased the volume (62 and 76 %) and total acidity (23 and 50%) of gastric Abstract ! Plectranthus barbatus Andr. is one of the most important species of the genus Plectranthus L′ Herit. (Lamiaceae), with a wide variety of traditional medicinal uses in Hindu and Ayurvedic traditional medicine as well as in the folk medicine of Brazil, tropical Africa and China. The plant has therefore been an attractive target for intensive chemical and pharmacological studies up to now. This review presents data about the phytochemistry, ethnobotanical uses and pharmacology of Plectranthus barbatus as well as the pharmacology of its constituents. In addition to essential oil, abietane diterpenoids and 8,13-epoxy-labd-14-en-11-one diterpenoids are the main constituents found in Plectranthus barbatus. The major ethnobotanical uses are for intestinal disturbance and liver fatigue, respiratory disorders, heart diseases and certain nervous system disorders. Forskolin as one of the major constituents with its unique adenylyl cyclase activation that underlies the wide range of pharmacologic...

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Section: Forskolinmentioning

confidence: 99%

Plectranthus barbatus: A Review of Phytochemistry, Ethnobotanical Uses and Pharmacology – Part 2

Alasbahi

Melzig²

2010

Planta Med

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“…Nakano et al, 1992). Numerous studies have found that stimulation of adenyl cyclase (Gregory et al, 1981;Burstein et al, 1984;Lee et al, 1984;Mittag & Tormay, 1985Nilsson et al, 1986;Bartels et al, 1987;Mittag et al, 1987Mittag et al, , 1993a or inhibition of cAMP phosphodiesterase (Mishima et al, 1991;Mittag et al, 1993a) in the ciliary epithelium lowers intraocular pressure. Conversely, inhibition of adenyl cyclase has been shown to decrease cAMP levels in the ciliary epithelium (Tobin & Osborne, 1989) and increase intraocular pressure (Meyer-Bothling et al, 1993).…”

Section: Aqueous Productionmentioning

confidence: 99%

Specialized neuropeptide Y- and glucagon-like immunoreactive amacrine cells in the peripheral retina of the turtle

Wetzel

Eldred

1997

Vis Neurosci

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There are many regional differences in cell morphology and neurochemistry in the retina. This study examined a specialized population of neuropeptide Y-and glucagon-like immunoreactive amacrine cells in the peripheral retina of the turtle. Some of the dendritic processes from these peptidergic amacrine cells formed a dense circumferentially oriented nerve fiber plexus which ran parallel to the ora serrata. Collaterals from this plexus projected into and innervated the nonpigmented ciliary epithelium in the pars plana region of the ciliary body. Electron microscopy revealed that the neuropeptide Y-and glucagon-like immunoreactive processes in the ciliary epithelium contained many labeled, large dense-cored vesicles. Small crystals of lipid-soluble fluorescent dye were implanted in the retina near the ora serrata in fixed retinal tissue to search for other peripheral retinal specializations. Numerous thick and thin cell processes oriented parallel to the ora serrata were labeled in the retina by the dye. In addition, many dye-labeled somata with circumferentially oriented dendritic arborizations were seen in the extreme periphery of the retina. Many of these dye-labeled cells and processes were clearly not associated with the neuropeptide Y-and glucagon-like immunoreactive cells described above. This study has shown that some peptidergic neurons in the peripheral retina have a unique morphology in comparison to more centrally located cells. The function of these specialized peripheral cells is not established, but the innervation of the ciliary epithelium by peptidergic amacrine cells suggests that they may be involved in control of aqueous inflow.

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“…Since intraocular pressure (IOP) is a function of the balance between fluid input and drainage out of the globe, the strategies for the treatment of open-angle glaucoma fall into two classes: reduction of aqueous humor secretion and enhancement of aqueous outflow (1)(2)(3)(4)(5)(6)(7)(8). Cholinomimetics, aagonists and b-blockers have been found to be useful in reducing IOP, and the clinical application of these agents has been well established in patients with glaucoma (1)(2)(3)(4)(5)(6)(7)(8). However, little is known about the signal transduction underlying postreceptor adrenergic and cholinergic processes in a discrete portion in the eye, partly due to the lack of a versatile yet sensitive assay of adenylate cyclase activity for the minute tissue mass (9)(10)(11).…”

Section: Introductionmentioning

confidence: 99%

Measurement of adenylate cyclase activity in the minute bovine ciliary epithelial cells during the pharmacological stimulation of adrenergic and cholinergic receptors

Sawada

Sugiyama

Kashiwagi

et al. 1999

J. Clin. Lab. Anal.

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Although essential to the secretion of aqueous humor, little is known about the signal transduction underlying postreceptor adrenergic and cholinergic processes in the ciliary epithelium. We adopted a highly sensitive fluorometric assay technique in order to examine adenylate cyclase activity in minute membrane preparations made from the bovine ciliary epithelial cells. The protein concentration of the preparation was 3-5 mg/ ml. Norepinephrine (10-7 , 10-6 and 10-5 M) and carbachol (10-7 and 10-5 M) were incubated with 10 ml of membrane preparation to analyze the extent of the receptor-coupled influences on the adenylate cyclase activity. Meanwhile, forskolin (10-5 M) was used to estimate the maximum adenylate cyclase activity. After the initial enzymatic destruction of noncyclic adenine nucleotides and phosphorylated metabolites, the diester linkage of cyclic AMP was cleaved and then converted to ATP. The ATP was enzymatically amplified to about 10,000 times of fructose-6-phosphate. The NADPH, formed when the fructose-6-phosphate was converted to 6-phosphogluconolactone, was measured fluorometrically. Basal and forskolin-stimulated maximum adenylate cyclase activities (pmol/mg protein/min) were 29.6 ± 7.6 and 86.6 ± 7.2 (mean ± SE), respectively. Norepinephrine increased the adenylate cyclase activity in a dose-dependent manner, while carbachol hardly affected the activity. These results indicate that the adenylate cyclase activity can be measured in the minute ciliary epithelial cells and, moreover, that the current assay can be applied to assess the efficacy of newly available ophthalmic solutions or systemic drugs influencing adenylate cyclase activity in a discrete portion in the eye.

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The effects of forskolin on cyclic AMP, intraocular pressure and aqueous humor formation in rabbits

Cited by 25 publications

References 19 publications

Plectranthus barbatus: A Review of Phytochemistry, Ethnobotanical Uses and Pharmacology – Part 2

Plectranthus barbatus: A Review of Phytochemistry, Ethnobotanical Uses and Pharmacology – Part 2

Specialized neuropeptide Y- and glucagon-like immunoreactive amacrine cells in the peripheral retina of the turtle

Measurement of adenylate cyclase activity in the minute bovine ciliary epithelial cells during the pharmacological stimulation of adrenergic and cholinergic receptors

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