β‐Lumicolchicine Interacts with the Benzodiazepine Binding Site to Potentiate GABA_A Receptor‐Mediated Currents

Abstract

An analogue of colchicine,β‐lumicolchicine, does not bind tubulin or disrupt microtubules. However, this compound is not pharmacologically completely inactive. β‐Lumicolchicine was found to competitively inhibit [3H]flunitrazepam binding and to enhance muscimol‐stimulated 36Cr‐uptake in mouse cerebral cortical microsacs. It also markedly potentiated GABA responses in Xenopusoocytes expressing human α1β2γ2S, but not α1β2, GABAA receptor subunits; this potentiation was reversed by the benzodiazepine receptor antagonist flumazenil. These results strongly suggest a direct effect of β‐Lumicolchicine on the GABAA receptor/chloride channel complex and caution that it possesses pharmacological effects, despite its inability to disrupt microtubules. Furthermore, β‐Lumicolchicine is structurally unrelated to benzodiazepines or quinolines and may provide a novel approach to the synthesis of ligands for this receptor.

Hepatoprotective activity of sea cucumber Phyllophorus sp. extract in carp (Cyprinus carpio)

“…The liver tissue of histology observation in treatment B acetic shown heavy damages histopathology alteration such as pyknosis and oedema. Injection of acetic acid in common carp lip as pain stimulus shown abnormal swimming ability [8] and increased or decreased regulation of code gene receptor kainite glutamatergic and cannabionid CB1 and neuthropic derivate factor in brain [9]. Pyknosis was one of cell death sign at necrosis, which chromatin in nucleolus unionized and cell membrane shrinked.…”

“…GABA is ionization, inhibiting neurotransmission in Central Neuron System (CNS) [14]. Inhibition of neurotransmitter in receptor decreased nerve system excitability, then caused incoordination, sedation, and anesthesia [8]. Light level damages in liver might be caused by inhibition of nerve system to decreased response pain stimulus in carp fish.…”