Abstract：
BACKGROUND AND PURPOSE:Muscarinic toxins (MTs) are snake venom peptides named for their ability to interfere with ligand binding to muscarinic acetylcholine receptors (mAChRs). Recent data infer that these toxins may have other G-protein-coupled receptor targets than the mAChRs. The purpose of this study was to systematically investigate the interactions of MTs with the adrenoceptor family members. EXPERIMENTAL APPROACH:We studied the interaction of four common MTs, MT1, MT3, MT7 and MTα, with cloned receptors expressed in insect cells by radioligand binding. Toxins showing modest to high-affinity interactions with adrenoceptors were additionally tested for effects on functional receptor responses by way of inhibition of agonist-induced Ca²⁺ increases. KEY RESULTS:All MTs behaved non-competitively in radioligand displacement binding. MT1 displayed higher binding affinity for the human α(2B)-adrenoceptor (IC₅₀ = 2.3 nM) as compared with muscarinic receptors (IC₅₀ ≥ 100 nM). MT3 appeared to have a broad spectrum of targets showing high-affinity binding (IC₅₀ = 1-10 nM) to M₄ mAChR, α(1A)-, α(1D)- and α(2A)-adrenoceptors and lower affinity binding (IC₅₀ ≥ 25 nM) to α(1B)- and α(2C)-adrenoceptors and M₁ mAChR. MT7 did not detectably bind to other receptors than M₁, and MTα was specific for the α(2B)-adrenoceptor. None of the toxins showed effects on β₁- or β₂-adrenoceptors. CONCLUSIONS AND IMPLICATIONS:Some of the MTs previously found to interact predominantly with mAChRs were shown to bind with high affinity to selected adrenoceptor subtypes. This renders these peptide toxins useful for engineering selective ligands to target various adrenoceptors.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Näreoja K,Kukkonen JP,Rondinelli S,Toivola DM,Meriluoto J,Näsman Jdoi
10.1111/j.1476-5381.2011.01468.xsubject
Has Abstractpub_date
2011-09-01 00:00:00pages
538-50issue
2beissn
0007-1188issn
1476-5381journal_volume
164pub_type
杂志文章abstract：:1. Diabetes mellitus produces marked abnormalities in motor nerve conduction, but the mechanism is not clear. In the present study we hypothesized that in the streptozotocin (STZ)-induced diabetic rat impaired vasodilator function is associated with reduced endoneural blood flow (EBF) which may contribute to nerve dys...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0702856
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journal_title：British journal of pharmacology
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journal_title：British journal of pharmacology
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journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1979.tb10837.x
更新日期：1979-07-01 00:00:00
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journal_title：British journal of pharmacology
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journal_title：British journal of pharmacology
pub_type： 杂志文章
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doi：10.1038/sj.bjp.0706115
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pub_type： 杂志文章
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journal_title：British journal of pharmacology
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doi：10.1111/j.1476-5381.2009.00454.x
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journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1990.tb12956.x
更新日期：1990-03-01 00:00:00
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pub_type： 杂志文章,评审
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journal_title：British journal of pharmacology
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doi：10.1111/j.1476-5381.1973.tb08384.x
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pub_type： 杂志文章
doi：10.1111/j.1476-5381.1980.tb10896.x
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pub_type： 杂志文章
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journal_title：British journal of pharmacology
pub_type： 杂志文章
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更新日期：2011-03-01 00:00:00
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pub_type： 杂志文章
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更新日期：1997-10-01 00:00:00
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journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1996.tb15460.x
更新日期：1996-06-01 00:00:00
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journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1977.tb08429.x
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