The natural β-carbolines facilitate inositol phosphate accumulation by activating small G-proteins in human neuroblastoma cells (SH-SY5Y)

Endogenous β‐Carbolines as Clonidine‐Displacing Substances

“…Furthermore, radioligand‐binding studies have suggested that harmane and norharmane bind to an unknown high‐affinity site in the brain34 and adrenal glands 27. In 1997, Lichtenberg‐Kraag and coworkers30 showed that harmane and norharmane could activate small G‐proteins in a human neuroblastoma cell line and that this effect was dose‐dependent with a bell‐shaped dose‐response curve. The SHSY5Y cell expressed a high‐affinity [ 3 H]norharmane site, and it has been concluded that activation of this β‐carboline receptor facilitates phosphoinositide‐specific phospholipase C activation by the muscarinic agonist carbachol 30.…”

“…In 1997, Lichtenberg‐Kraag and coworkers30 showed that harmane and norharmane could activate small G‐proteins in a human neuroblastoma cell line and that this effect was dose‐dependent with a bell‐shaped dose‐response curve. The SHSY5Y cell expressed a high‐affinity [ 3 H]norharmane site, and it has been concluded that activation of this β‐carboline receptor facilitates phosphoinositide‐specific phospholipase C activation by the muscarinic agonist carbachol 30. In a different study, norharmane and harmane were shown to activate G‐proteins in a receptor‐independent manner with EC50 values of 60 μM and 300 μM, respectively 31.…”

Thermodynamic Study of Small Hydrophobic Ions at the Water–Lipid Interface

“…The activity coefficient = , [6] where the parameter is known as an apparent partition parameter (34). Similarly, in the binding model when α/R * i → 0, γ ≈ 1, and the term (N (α/R * i )) in the denominator (see Eq.…”

“…Also, it has been suggested that GTP-binding proteins can be involved in the facilitating action of the β-carbolines (6), which points to a drug-membrane interaction event as a first target of a specific signal transduction pathway.…”

“…Here, we report thermodynamic studies of the binding of fluorescent hydrophobic ions such as norharman (Nor) (derivative of β-carboline 9H-pyrido [3,[4][5][6]indole) and tryptophan (Trp) to neutral and negatively charged small unilamellar vesicles (SUVs) composed of either dimyristoylphosphatidylcholine (DMPC) or dimyristoylphosphatidic acid (DMPA) and dimyristoyl phosphatidylglycerol (DMPG) with different proportions of anionic lipid and at different ionic strengths. Both Nor and Trp (Scheme 1), are small amphipathic molecules with the dual intrinsic charged and hydrophobic features.…”