Characterization of a Novel Iodocyanopindolol and SM-11044 Binding Protein, Which May Mediate Relaxation of Depolarized Rat Colon Tonus

Sugasawa, Toshinari; Matsuzaki-Fujita, Masago; Guillaume, Jean‐Luc; Camoin, Luc; Morooka, Shigenori; Strosberg, A. D.

doi:10.1074/jbc.272.34.21244

Cited by 9 publications

(6 citation statements)

References 28 publications

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“…This is entirely consistent with the low β 3 -adrenoceptor affinity of unlabeled alprenolol (Hoffmann et al 2004 (Roberts et al 1993). Moreover, at high concentrations, [ 125 I]-iodocyanopindolol may also bind to α 1 -adrenoceptors (Brahmadevara et al 2004), serotonin receptors (Hoyer et al 1985), and other nonadrenergic sites (Sugasawa et al 1997). Taken together, these problems make the detection of β 3 -adrenoceptors in tissues expressing mixed β-adrenoceptor subtype populations almost impossible.…”

Section: Detection Of β 3 -Adrenoceptorssupporting

confidence: 55%

Tools to study β3-adrenoceptors

Vrydag

Michel

2007

Naunyn-Schmied Arch Pharmacol

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β 3 -adrenoceptors mediate some of the effects of catecholamines on tissues such as blood vessels or the urinary bladder and are putative targets for the treatment of diseases such as the overactive bladder syndrome. Progress in the understanding of the presence, function, and regulation of β 3 -adrenoceptors has been hampered by a lack of highly specific tools. "Classical" is not selective for β 3 -adrenoceptors, at least in humans, and may actually be a partial agonist. Radioligands, which are suitable either for the selective labeling of β 3 -adrenoceptors or for the nonselective labeling of all β-adrenoceptor subtypes, are also missing. β 3 -and β 1 /β 2 double knockout mice have been reported, but their usefulness for extrapolations in humans is questionable based upon major differences between humans and rodents with regard to the ligand recognition and expression profiles of β 3 -adrenoceptors. While the common availability of more selective agonists and antagonists at the β 3 -adrenoceptor is urgently awaited, the limitations of the currently available tools need to be considered in studies of β 3 -adrenoceptor for the time being.

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Section: Detection Of β 3 -Adrenoceptorssupporting

confidence: 55%

Tools to study β3-adrenoceptors

Vrydag

Michel

2007

Naunyn-Schmied Arch Pharmacol

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“…Secondly, SR 59,230A competed for more [ 125 I]-ICYP sites than any other ligand tested here and hence also for many sites defined as non-specific based on isoprenaline competition. We do not know what these sites represent, but a low affinity [ 125 I]-ICYP binding site insensitive, e.g., to BRL 37,344 has been reported in rat colon (Sugasawa et al, 1997). Thirdly, although non-iodinated cyanopindolol competition curves were not significantly better explained by a two-site model in most experiments, they were very shallow in bladder (but not lung).…”

Section: Discussionmentioning

confidence: 99%

Can [125I]-Iodocyanopindolol Label β3-Adrenoceptors in Rat Urinary Bladder?

Schneider¹,

Michel²

2010

Front. Pharm.

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β3-Adrenoceptors have been demonstrated to mediate urinary bladder smooth muscle relaxation but proof of their expression at the protein level has been missing because of lack of suitable antibodies or radioligands. As among various available radioligands [125I]-iodocyanopindolol ([125I]-ICYP) exhibited the smallest problems in labeling cloned human β3-adrenoceptors in previous studies, we have explored its suitability to label β3-adrenoceptors in rat urinary bladder in saturation and competition radioligand binding experiments. Rat lung was used as an internal control and exhibited all characteristics expected from this tissue with regard to β1/β2-adrenoceptor labeling. Saturation and competition binding studies with [125I]-ICYP in rat bladder yielded saturable binding sites with an affinity compatible with β3-adrenoceptors. In competition experiments various agonists and antagonists largely exhibited a profile compatible with a population consisting largely of β3-adrenoceptors. However, the binding competition properties of ICI 118,551 and SR 59,230A were not easily explained by the idea of labeling a homogeneous β3-adrenoceptor population but interpretation of the data was limited by a high degree of non-specific binding in [125I]-ICYP concentrations required to label the receptors. We conclude that [125I]-ICYP can be used to label tissue β3-adrenoceptors but results obtained with this ligand have to be interpreted with caution.

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“…(Niclauß, Michel-Reher, Alewijnse, & Michel, 2006). The high concentrations required to use them as labels for β 3 -adrenoceptors imply saturation of the other two subtypes, high non-specific binding and binding to non-β-adrenoceptor sites including 5-HT receptors (Hoyer, Engel, & Kalkman, 1985a,b) and a protein later identified as a member of the TM9SF multi-spanning membrane protein family (Sugasawa et al, 2001(Sugasawa et al, , 1997. Thus, only one group has extensively used [ 3 H]-CGP 12,177 in intact transfected cells (Baker, 2005(Baker, , 2010.…”

Section: Changes In G Proteins Ac and Pdesmentioning

confidence: 99%

“…Standard β‐adrenoceptor radioligands such as [ 3 H]‐CGP 12,177 or [ 125 I]‐iodocyanopindolol have much lower affinity for β 3 ‐adrenoceptors as compared to β 1 ‐ and β 2 ‐adrenoceptors (Niclauß, Michel‐Reher, Alewijnse, & Michel, ). The high concentrations required to use them as labels for β 3 ‐adrenoceptors imply saturation of the other two subtypes, high non‐specific binding and binding to non‐β‐adrenoceptor sites including 5‐HT receptors (Hoyer, Engel, & Kalkman, ,b) and a protein later identified as a member of the TM9SF multi‐spanning membrane protein family (Sugasawa et al, , ). Thus, only one group has extensively used [ 3 H]‐CGP 12,177 in intact transfected cells (Baker, , ).…”

Section: Changes In β3‐adrenoceptor Protein Expression Phosphorylatimentioning

confidence: 99%

Agonist‐induced desensitisation of β₃‐adrenoceptors: Where, when, and how?

Okeke

Angers

Bouvier

et al. 2019

British J Pharmacology

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β3‐Adrenoceptor agonists have proven useful in the treatment of overactive bladder syndrome, but it is not known whether their efficacy during chronic administration may be limited by receptor‐induced desensitisation. Whereas the β2‐adrenoceptor has phosphorylation sites that are important for desensitisation, the β3‐adrenoceptor lacks these; therefore, it had been assumed that β3‐adrenoceptors are largely resistant to agonist‐induced desensitisation. While all direct comparative studies demonstrate that β3‐adrenoceptors are less susceptible to desensitisation than β2‐adrenoceptors, desensitisation of β3‐adrenoceptors has been observed in many models and treatment settings. Chimeric β2‐ and β3‐adrenoceptors have demonstrated that the C‐terminal tail of the receptor plays an important role in the relative resistance to desensitisation but is not the only relevant factor. While the evidence from some models, such as transfected CHO cells, is inconsistent, it appears that desensitisation is observed more often after long‐term (hours to days) than short‐term (minutes to hours) agonist exposure. When it occurs, desensitisation of β3‐adrenoceptors can involve multiple levels including down‐regulation of its mRNA and the receptor protein and alterations in post‐receptor signalling events. The relative contributions of these mechanistic factors apparently depend on the cell type under investigation. Which if any of these factors is applicable to the human urinary bladder remains to be determined. Linked Articles This article is part of a themed section on Adrenoceptors—New Roles for Old Players. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.14/issuetoc

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Characterization of a Novel Iodocyanopindolol and SM-11044 Binding Protein, Which May Mediate Relaxation of Depolarized Rat Colon Tonus

Cited by 9 publications

References 28 publications

Tools to study β3-adrenoceptors

Tools to study β3-adrenoceptors

Can [125I]-Iodocyanopindolol Label β3-Adrenoceptors in Rat Urinary Bladder?

Agonist‐induced desensitisation of β₃‐adrenoceptors: Where, when, and how?

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Characterization of a Novel Iodocyanopindolol and SM-11044 Binding Protein, Which May Mediate Relaxation of Depolarized Rat Colon Tonus

Cited by 9 publications

References 28 publications

Tools to study β3-adrenoceptors

Tools to study β3-adrenoceptors

Can [125I]-Iodocyanopindolol Label β3-Adrenoceptors in Rat Urinary Bladder?

Agonist‐induced desensitisation of β3‐adrenoceptors: Where, when, and how?

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Product

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Agonist‐induced desensitisation of β₃‐adrenoceptors: Where, when, and how?