Autonomic Nervous System: Adrenergic Agonists

Sears, Marvin L.

doi:10.1007/978-3-642-69222-2_5

Cited by 43 publications

(18 citation statements)

References 227 publications

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“…Water is released at that surface through aquaporin AQP1 and AQP4 channels (10,45). The aquaporins at the apical surface of the NPE cells may provide an uptake pathway for water under conditions when the virtual space between the PE and NPE cells accumulates fluid (42). Aquaporins have not yet been identified in PE cells (11).…”

mentioning

confidence: 99%

Regulation of gap junction coupling in bovine ciliary epithelium

Wang

Wai

Valiūnas

et al. 2010

American Journal of Physiology-Cell Physiology

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Aqueous humor is formed by fluid transfer from the ciliary stroma sequentially across the pigmented ciliary epithelial (PE) cells, gap junctions, and nonpigmented ciliary epithelial (NPE) cells. Which connexins (Cx) contribute to PE-NPE gap junctional formation appears species specific. We tested whether small interfering RNA (siRNA) against Cx43 (siCx43) affects bovine PE-NPE communication and whether cAMP affects communication. Native bovine ciliary epithelial cells were studied by dual-cell patch clamping, Lucifer Yellow (LY) transfer, quantitative polymerase chain reaction with reverse transcription (qRT-PCR), and Western immunoblot. qRT-PCR revealed at least 100-fold greater expression for Cx43 than Cx40. siCx43 knocked down target mRNA expression by 55 ± 7% after 24 h, compared with nontargeting control siRNA (NTC1) transfection. After 48 h, siCx43 reduced Cx43 protein expression and LY transfer. The ratio of fluorescence intensity (Rf) in recipient to donor cell was 0.47 ± 0.09 ( n = 11) 10 min after whole cell patch formation in couplets transfected with NTC1. siCx43 decreased Rf by ∼60% to 0.20 ± 0.07 ( n = 13, P < 0.02). Dibutyryl-cAMP (500 μM) also reduced LY dye transfer by ∼60%, reducing Rf from 0.41 ± 0.05 ( n = 15) to 0.17 ± 0.05 ( n = 20) after 10 min. Junctional currents were lowered by ∼50% ( n = 6) after 10-min perfusion with 500 μM dibutyryl-cAMP ( n = 6); thereafter, heptanol abolished the currents ( n = 5). Preincubation with the PKA inhibitor H-89 (2 μM) prevented cAMP-triggered current reduction ( n = 6). We conclude that 1) Cx43, but not Cx40, is a major functional component of bovine PE-NPE gap junctions; and 2) under certain conditions, cAMP may act through PKA to inhibit bovine PE-NPE gap junctional communication.

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confidence: 99%

Regulation of gap junction coupling in bovine ciliary epithelium

Wang

Wai

Valiūnas

et al. 2010

American Journal of Physiology-Cell Physiology

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“…Unlike topical cholinergic (Kaufman et al, 1984) and adrenergic agents (Sears, 1984), flunarizine did not affect PD; various drugs that reduce IOP, for instance several ␣-and ␤-adrenergic blockers, have been shown not to alter pupil size of rabbits (Lotti et al, 1984). Moreover, flunarizine also appeared to be well tolerated because it caused no ocular inflammatory response.…”

Section: Discussionmentioning

confidence: 91%

“…This model is particularly useful for locating prejunctional drug effects (Jumblatt and North, 1986;Ogidigben et al, 1994;Russell and Potter, 2001) and may provide clues to cellular sites and mechanisms of action of compounds intended to reduce IOP. The iris and ciliary body are innervated by the sympathetic and parasympathetic autonomic nervous systems, which control aqueous humor formation and drainage (Kaufman et al, 1984;Sears, 1984). Several drugs used to control ocular hypertension, which is frequent in glaucoma (Leopold and Duzman, 1986), act prejunctionally by affecting neurotransmitter release from nerve terminals.…”

Section: Discussionmentioning

confidence: 99%

Ocular Hypotensive Action of Topical Flunarizine in the Rabbit: Role of ς₁Recognition Sites

Campana

Bucolo

Murari

et al. 2002

J Pharmacol Exp Ther

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In a previous study we ascertained the presence of 1 and 2 recognition sites in the rabbit iris-ciliary body, an ocular structure involved in aqueous humor production and drainage. We characterized the 1 sites using the preferential ligand (ϩ)-pentazocine, which caused a significant reduction of intraocular pressure (IOP). In the present study, flunarizine, a calcium channel blocker with a complex pharmacological profile, bound to 1 sites expressed in the iris-ciliary body with moderate affinity (K i ϭ 68 nM). Unilateral topical flunarizine (0.01-0.1%) caused a dose-related reduction of IOP in ocular normotensive rabbits and in the ␣-chymotrypsin model of ocular hypertension, without altering the IOP of the contralateral eye. This activity was blocked by the 1 site antagonist NE-100 [N,Ndipropyl-2-[4-methoxy-3-(2-phenylethoxy)phenyl]ethylamine HCl] which, by itself, had no effect on IOP. Detection of flunarizine in rabbit iris-ciliary body homogenates, after topical instillation, showed that it adequately penetrates the rabbit eye. To investigate mechanisms that may contribute to ocular hypotension induced by 1 agonists, we carried out in vitro studies on the isolated rabbit iris-ciliary body. Sigma () recognition sites are a unique class of binding sites, heterogeneously distributed in the nervous system and in peripheral organs, that presumably serve as receptors for some unidentified endogenous ligand (Walker et al., 1990;Quiron et al., 1992). The recognition sites bind an array of structural classes of compounds including haloperidol, 1,3-di-O-tolylguanidine (DTG), and (ϩ)-benzomorphans, such as (ϩ)-pentazocine and (ϩ)-N-allylnormetazocine (Su and Junien, 1994). On the basis of biochemical and radioligand binding data, recognition sites have been classified into at least two types, 1 and 2 (Quiron et al., 1992). The 1 recognition sites display preferential affinity and stereoselectivity for (ϩ)-benzomorphans . A 1 binding protein has been cloned (Hanner et al., 1996), and its sequence shows significant similarities with sterol C 8 -C 7 isomerases from fungi.The functional role of recognition sites and the cellular mechanisms responsible for the effects produced by -site ligands have not been clearly determined, although these compounds may act as neuromodulators. Previous reports have associated -site ligands with calcium homeostasis (Brent et al., 1996;Hayashi et al., 2000;Hayashi and Su, 2001). -site ligands can influence [ 3 H]dopamine and [ 3 H]norepinephrine (NE) release from rat brain slices, acting, at least partially, presynaptically (Gonzalez-Alvear and Werling, 1995;Gonzalez and Werling, 1997).Several -site ligands influence electrically evoked contractions in the guinea pig longitudinal muscle/myenteric plexus preparation (Campbell et al., 1989). These latter findings add evidence to the theory that recognition sites participate in the regulation of autonomic functions and that -site ligands may interfere with neurotransmitter release, modulating their action on innervated tissue (Su and J...

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“…The metabolic requirements of these avascular ocular structures are satisfied by an aqueous humor produced by the ciliary epithelium of the ciliary body of the eye [9]. This epithelium is a bilayered structure that acts on the substrates of water, salt, and protein in the stroma of the ciliary processes to secrete an aqueous humor into the posterior chamber by active transport.…”

Section: Imentioning

confidence: 99%

Immunohistochemistry of Intercellular Junctions in Developing Ciliary Body of the Rabbit Eye.

Nakano

Sears

1997

Acta Histochem. Cytochem

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Autonomic Nervous System: Adrenergic Agonists

Cited by 43 publications

References 227 publications

Regulation of gap junction coupling in bovine ciliary epithelium

Regulation of gap junction coupling in bovine ciliary epithelium

Ocular Hypotensive Action of Topical Flunarizine in the Rabbit: Role of ς₁Recognition Sites

Immunohistochemistry of Intercellular Junctions in Developing Ciliary Body of the Rabbit Eye.

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Autonomic Nervous System: Adrenergic Agonists

Cited by 43 publications

References 227 publications

Regulation of gap junction coupling in bovine ciliary epithelium

Regulation of gap junction coupling in bovine ciliary epithelium

Ocular Hypotensive Action of Topical Flunarizine in the Rabbit: Role of ς1Recognition Sites

Immunohistochemistry of Intercellular Junctions in Developing Ciliary Body of the Rabbit Eye.

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Ocular Hypotensive Action of Topical Flunarizine in the Rabbit: Role of ς₁Recognition Sites