Endogenous neurosteroids and their synthetic analogues-neuroactive steroids-have been found to bind to muscarinic acetylcholine receptors and allosterically modulate acetylcholine binding and function. Using radioligand binding experiments we investigated their binding mode. We show that neuroactive steroids bind to two binding sites on muscarinic receptors. Their affinity for the high-affinity binding site is about 100 nM. Their affinity for the low-affinity binding site is about 10 µM. The high-affinity binding occurs at the same site as binding of steroid-based WIN-compounds that is different from the common allosteric binding site for alcuronium or gallamine that is located between the second and third extracellular loop of the receptor. This binding site is also different from the allosteric binding site for the structurally related aminosteroid-based myorelaxants pancuronium and rapacuronium. Membrane cholesterol competes with neurosteroids/neuroactive steroids binding to both high- and low-affinity binding site, indicating that both sites are oriented towards the cell membrane..

• MeSH
• alosterická regulace účinky léků   fyziologie   MeSH
• androstany metabolismus   farmakologie   MeSH
• androsteny metabolismus   farmakologie   MeSH
• benzimidazoly metabolismus   farmakologie   MeSH
• CHO buňky MeSH
• cholesterol metabolismus   MeSH
• Cricetulus MeSH
• křečci praví MeSH
• lidé MeSH
• nervosvalové látky nedepolarizující metabolismus   farmakologie   MeSH
• neurosteroidy metabolismus   MeSH
• receptory muskarinové metabolismus   MeSH
• triethojodid gallaminia metabolismus   farmakologie   MeSH
• vazebná místa účinky léků   fyziologie   MeSH
• vekuronium analogy a deriváty   metabolismus   farmakologie   MeSH
• zvířata MeSH
• Check Tag
• křečci praví MeSH
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• MeSH
• alkuronium farmakologie   metabolismus   MeSH
• jedy farmakologie   metabolismus   MeSH
• krysa rodu rattus MeSH
• myokard metabolismus   ultrasonografie   MeSH
• receptory muskarinové metabolismus   účinky léků   MeSH
• skopolaminové deriváty metabolismus   MeSH
• strychnin farmakologie   metabolismus   MeSH
• triethojodid gallaminia farmakologie   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• zvířata MeSH
• Publikační typ
• srovnávací studie MeSH