The calcium –calmodulin‐dependent protein kinase kinase inhibitor, STO‐609, inhibits nicotine‐induced currents and intracellular calcium increase in insect neurosecretory cells

Dorsal unpaired median neurons are insect neurosecretory cells that express alpha-bungarotoxin ( α-Bgt)-sensitive and -insensitive nicotinic acetylcholine receptors (nAChRs) subtypes. We found that the calmodulin kinase kinase (CaMKK) selective inhibitor STO reduced nicotinic currents, and strongly when co-applied with α-Bgt. Interestingly, intracellular application of the AMPK activator, A-7 6, prevented the reduction in nicotine-induced currents observed in the presence of the AMPK inhibitor, DM. STO prevented the increase in intracellular calcium induced by nicotine. Moreover, currents induced by the benzamide compound, LMA, which acts as a specific activator of nAChR2 subtype, were b locked by mecamylamine. We suggested that nAChR2 could be considered as a mediated receptor. AMPK, AMP-activated protein kinase; DM, dorsomorphin; STO, STO-609 7-oxo-7H-benzimidazo[2,1-a] benz[de]isoquinoline-3-carboxylic acid. AbstractInsect neuronal nicotinic acetylcholine receptors (nAChRs) are transmembrane receptors that play a key role in the development and synaptic plasticity of both vertebrates and invertebrates and are considered to be major targets of neonicotinoid insecticides. We used dorsal unpaired median (DUM) neurons, which are insect neurosecretory cells, in order to explore the intracellular mechanisms leading to the regulation of insect neuronal nAChRs in more detail. Using whole-cell patch-clamp and fura-2AM calcium imaging techniques, we found that a novel CaMKK/AMPK p...
Source: Journal of Neurochemistry - Category: Neuroscience Authors: Tags: ORIGINAL ARTICLE Source Type: research