ETB Receptor Activates Adenylyl Cyclase via a c-PLA2-Dependent Mechanism: A Novel Counterregulatory Mechanism of ET-Induced Contraction in Airway Smooth Muscle

El‐Mowafy, Abdalla M.; Biggs, David F.

doi:10.1006/bbrc.2001.5389

Cited by 8 publications

(5 citation statements)

References 31 publications

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“…There are several ways in which endothelin and/or Gαq signaling might feed into known pigmentation pathways. For instance, Ednrb has been shown to activate adenylyl cyclase in rabbit tracheal smooth muscle (El‐Mowafy and Biggs, 2001) and phosphorylate CREB via the MAP kinase signaling pathway in rat astrocytes (Schinelli et al., 2001).…”

Section: Discussionmentioning

confidence: 99%

Independent regulation of hair and skin color by two G protein‐coupled pathways

Raamsdonk

Barsh

Wakamatsu

et al. 2009

Pigment Cell Melanoma Res

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Hair color and skin color are frequently coordinated in mammalian species. To explore this, we have studied mutations in two different G protein coupled pathways, each of which affects the darkness of both hair and skin color. In each mouse mutant (Gnaq(Dsk1), Gna11(Dsk7), and Mc1r(e)), we analyzed the melanocyte density and the concentrations of eumelanin (black pigment) and pheomelanin (yellow pigment) in the hair or skin to determine the mechanisms regulating pigmentation. Surprisingly, we discovered that each mutation affects hair and skin color differently. Furthermore, we have found that in the epidermis, the melanocortin signaling pathway does not couple the synthesis of eumelanin with pheomelanin, as it does in hair follicles. Even by shared signaling pathways, hair and skin melanocytes are regulated quite independently.

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Section: Discussionmentioning

confidence: 99%

Independent regulation of hair and skin color by two G protein‐coupled pathways

Raamsdonk

Barsh

Wakamatsu

et al. 2009

Pigment Cell Melanoma Res

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“…Zinc (II) protoporphyrin-IX (ZnPP, BIOMOL Research Laboratories, Inc., Plymouth Meeting, PA), an NOS (25) and sGC (26) inhibitor, KT-5823 (C 29 H 25 N 3 O 5 ) (BIOMOL), a specific inhibitor of PKG, 8-bromo-cGMP (BIOMOL), a cell membrane-permeable cGMP analog, 8-bromo-cAMP (BIOMOL), a cell membrane-permeable cAMP analog, 9-(tetrahydro-2Ј-furyl) adenine (SQ-22536) (BIOMOL), a cell membrane-permeable adenylate cyclase inhibitor, were added to the basal and apical compartments of the bicameral units on d 1 at the desired concentrations as shown in corresponding figure legends. The concentrations of the inhibitors used in our studies were selected as based on previously published reports (16,(27)(28)(29). These compounds, except ZnPP, which was replenished daily, were incubated with Sertoli cells for only 24 h and were removed by rinsing the cell epithelium with F12/DMEM (3ϫ) thereafter.…”

Section: Quantitative Analysis On the Sertoli Cell Tj-permeability Bamentioning

confidence: 99%

Regulation of Sertoli Cell Tight Junction Dynamics in the Rat Testis via the Nitric Oxide Synthase/Soluble Guanylate Cyclase/3′,5′-Cyclic Guanosine Monophosphate/Protein Kinase G Signaling Pathway: an in Vitro Study

2003

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Nitric oxide (NO) synthase (NOS) catalyzes the oxidation of L-arginine to NO. NO plays a crucial role in regulating various physiological functions, possibly including junction dynamics via its effects on cAMP and cGMP, which are known modulators of tight junction (TJ) dynamics. Although inducible NOS (iNOS) and endothelial NOS (eNOS) are found in the testis and have been implicated in the regulation of spermatogenesis, their role(s) in TJ dynamics, if any, is not known. When Sertoli cells were cultured at 0.5-1.2 x 10(6) cells/cm(2) on Matrigel-coated dishes or bicameral units, functional TJ barrier was formed when the barrier function was assessed by quantifying transepithelial electrical resistance across the cell epithelium. The assembly of the TJ barrier was shown to associate with a significant plummeting in the levels of iNOS and eNOS, seemingly suggesting that their presence by producing NO might perturb TJ assembly. To further confirm the role of NOS on the TJ barrier function in vitro, zinc (II) protoporphyrin-IX (ZnPP), an NOS inhibitor and a soluble guanylate cyclase inhibitor, was added to the Sertoli cell cultures during TJ assembly. Indeed, ZnPP was found to facilitate the assembly and maintenance of the Sertoli cell TJ barrier, possibly by inducing the production of TJ-associated proteins, such as occludin. Subsequent studies by immunoprecipitation and immunoblotting have shown that iNOS and eNOS are structurally linked to TJ-integral membrane proteins, such as occludin, and cytoskeletal proteins, such as actin, vimentin, and alpha-tubulin. When the cAMP and cGMP levels in these ZnPP-treated samples were quantified, a ZnPP-induced reduction of intracellular cGMP, but not cAMP, was indeed detected. Furthermore, 8-bromo-cGMP, a cell membrane-permeable analog of cGMP, could also perturb the TJ barrier dose dependently similar to the effects of 8-bromo-cAMP. KT-5823, a specific inhibitor of protein kinase G, was shown to facilitate the Sertoli cell TJ barrier assembly. Cytokines, such as TGF-beta and TNF-alpha, known to perturb the Sertoli cell TJ barrier, were also shown to stimulate Sertoli cell iNOS and eNOS expression dose dependently in vitro. Collectively, these results illustrate NOS is an important physiological regulator of TJ dynamics in the testis, exerting its effects via the NO/soluble guanylate cyclase/cGMP/protein kinase G signaling pathway.

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“…ET-1 may increase cholinergic transmission in the bronchus system [5], although atropine did not alter the contractile effect of ET-1 unequivocally, at least in the isolated guinea pig trachea [6]. The response curves were species-specific: in isolated guinea pig and rat tracheas, ET-1 induced a normal sigmoidal dose-response curve [7], [8], albeit in rabbit trachea muscle a bell-shaped curve was obvi-ous [9]. The adenylyl cyclase inhibitor SQ-22 536 changed the bell-shaped curve back to a normal sigmoidal curve.…”

mentioning

confidence: 99%

Thyme Extract, but not Thymol, Inhibits Endothelin-Induced Contractions of Isolated Rat Trachea

Engelbertz

Schwenk²,

Kinzinger³

et al. 2008

Planta Med

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Thyme extract is known to posses spasmolytic effects on isolated trachea and to increase ciliary activity. A small part of this effect is mediated via beta (2) receptors, but other receptors are supposed to be involved. Endothelin has a pathophysiological impact in asthma with respect to hyper-reagibility and contracting isolated trachea smooth muscles and was, therefore, investigated. Thyme extract inhibited endothelin-induced contraction. Emax decreased depending on the concentration of thyme extract indicating a non-competitive inhibition. Bosentan, an endothelin receptor antagonist (positive control), acted as a competitive inhibitor. The interaction/combination of thyme extract and bosentan was additive but not supra-additive indicating an interaction with the endothelin system. Thymol (one of the major compounds of thyme extract) did not interact with the endothelin system. It is concluded that thyme extract may help in diseases related to endothelin hyper-reagibility of the bronchus system such as asthma and COPD (chronic obstructive pulmonary disease), although thymol is not involved in this effect.

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ETB Receptor Activates Adenylyl Cyclase via a c-PLA2-Dependent Mechanism: A Novel Counterregulatory Mechanism of ET-Induced Contraction in Airway Smooth Muscle

Cited by 8 publications

References 31 publications

Independent regulation of hair and skin color by two G protein‐coupled pathways

Independent regulation of hair and skin color by two G protein‐coupled pathways

Regulation of Sertoli Cell Tight Junction Dynamics in the Rat Testis via the Nitric Oxide Synthase/Soluble Guanylate Cyclase/3′,5′-Cyclic Guanosine Monophosphate/Protein Kinase G Signaling Pathway: an in Vitro Study

Thyme Extract, but not Thymol, Inhibits Endothelin-Induced Contractions of Isolated Rat Trachea

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