[3H]BQ-123, a highly specific and reversible radioligand for the endothelin ETA receptor subtype.

Ihara, Masaki; Yamanaka, Rie; Ohwaki, Kenji; Ozaki, Satoshi; Fukami, Tatsuki; Ishikawa, Kiyofumi; Clifford, Merwyn; Yano, Mitsuo

doi:10.1016/s0021-5198(19)50811-3

Cited by 2 publications

(2 citation statements)

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“…In addition, sarafotoxin, a selective ET B receptor agonist (Heyl et al, 1993; Williams et al, 1991), did not induce relaxations in arteries transduced with AdCMVeNOS, suggesting that activation of ET A receptors located on the vascular adventitia is involved in the relaxations to ET-1 and ET-2. This concept is further supported by the present results showing that BQ-123, a selective ET A receptor antagonist (Douglas, Meek and Ohlstein, 1994; Ihara et al, 1995), almost abolished ET-1-induced relaxations, whereas BQ-788, a selective ET B receptor antagonist (Ishikawa et al, 1994; Karaki, Sudjarwo and Hori, 1994) was without effect. In our previous ex vivo and in vivo gene transfer studies on canine cerebral arteries, electron microscopy immunogold labeling indicated that expression of recombinant eNOS protein was localized to adventitial fibroblasts (Chen et al, 1997 a ; Tsutsui et al, 1998).…”

Section: Discussionsupporting

confidence: 81%

Adventitial Expression of Recombinant Endothelial Nitric Oxide Synthase Gene Reverses Vasoconstrictor Effect of Endothelin-1

Onoue

Tsutsui

Smith

et al. 1999

J Cereb Blood Flow Metab

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The present study was designed to determine the effect of recombinant endothelial nitric oxide synthase (eNOS) gene expression on reactivity of canine basilar arteries to endothelin-1 (ET-1). Experiments were performed ex vivo. The arteries were exposed (30 minutes at 37 degrees C) to adenoviral vectors encoding eNOS gene (AdCMVeNOS) or beta-galactosidase reporter gene (AdCMVbeta-Gal). Twenty-four hours after transduction, transgene expression was evident mainly in the vascular adventitia. Rings of control (nontransduced), AdCMVbeta-Gal- and AdCMVeNOS-transduced arteries with and without endothelium were suspended for isometric tension recording. Levels of guanosine 3',5'-cyclic monophosphate (cGMP) were measured by radioimmunoassay. During contractions to uridine 5'-triphosphate, ET-1 (10(-10) to 3x10(-9) mol/L) caused further increase in tension in control and AdCMVbeta-Gal-transduced arteries. In contrast, ET-1 caused concentration-dependent relaxations of AdCMVeNOS-transduced arteries. The relaxations to ET-1 in AdCMVeNOS-transduced arteries were endothelium-independent. They were abolished by N(G)-nitro-L-arginine methyl ester or by chemical treatment of adventitia with paraformaldehyde before gene transfer. ET-1 (10(-9) mol/L) significantly increased intracellular cGMP levels in AdCMVeNOS-transduced arteries without endothelium. In arteries transduced with AdCMVeNOS, higher concentrations (10(-9) to 3x10(-8) mol/L) of ET-2 also caused relaxations, whereas ET-3 and sarafotoxin, a selective ET(B) receptor agonist, did not produce any relaxations. The relaxations to ET-1 in AdCMVeNOS-transduced arteries were strongly reduced by BQ-123 (10(-7) mol/L), an ET(A) receptor antagonist, but were not affected by BQ-788 (3x10(-7) mol/L), an ET(B) receptor antagonist. These results suggest that genetically modified adventitia can produce nitric oxide and cause relaxations in response to ET-1 via activation of ET(A) receptors. Our findings support a novel concept that successful transfer and expression of recombinant eNOS gene can lead to a qualitative change in responsiveness to vasoconstrictor substances.

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Section: Discussionsupporting

confidence: 81%

Adventitial Expression of Recombinant Endothelial Nitric Oxide Synthase Gene Reverses Vasoconstrictor Effect of Endothelin-1

Onoue

Tsutsui

Smith

et al. 1999

J Cereb Blood Flow Metab

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show abstract

“…Contraction to ET-1 is relatively slow to develop, but is persistent and resistant to reversal by washout. This may be explained in part by the pseudo-irreversible nature of ET-1 binding to ET receptors (NAMBI et al 1994;WAGGONER et al 1992;WU-WONG et al 1994;WATAKABE et al 1992;IHARA et al 1995), which causes sustained receptor activation and signal transduction, consistent with the persistence of elevated bronchial tone often seen in asthma.…”

Section: A) Direct Airway Smooth Muscle Contractionmentioning

confidence: 99%

Involvement of the Endothelins in Airway Reactivity and Disease

Goldie¹,

Henry²

2001

Endothelin and Its Inhibitors

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[3H]BQ-123, a highly specific and reversible radioligand for the endothelin ETA receptor subtype.

Cited by 2 publications

References 0 publications

Adventitial Expression of Recombinant Endothelial Nitric Oxide Synthase Gene Reverses Vasoconstrictor Effect of Endothelin-1

Adventitial Expression of Recombinant Endothelial Nitric Oxide Synthase Gene Reverses Vasoconstrictor Effect of Endothelin-1

Involvement of the Endothelins in Airway Reactivity and Disease

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