Modulation of metabotropic and ionotropic functions of the nicotinic α7 receptor by the intracellular domain

CHRESTIA, F.; KÖLHER, I.; BRUZZONE, A.; BOUZAT, C.; ESANDI, M.C.

Mar del Plata

Congreso; Reunión Anual de Sociedades de Biociencia 2019; 2019

The α7 receptor is a nicotinic receptor present in the nervous system and in non-neuronal cells. It has been demonstrated that α7 not only mediates fast synaptic transmission in neurons, but also regulates inflammatory responses in immune cell, neurite growth discovery. Essential oils (EOs) are natural products produced by aromatic plants. EOs are complex mixtures that usually contain two or three major phytochemicals, which can be terpenes and/or aromatic compounds. We used paralysis assays of wild-type and mutant C. elegans strain and electrophysiological recordings to identify EO with potential anthelmintic activities, reveal the active components, the target sites and mechanisms of action. We found that EOs belonging to six different orders produced rapid paralysis of C. elegans and we establish the half maximal effective concentration values between 0.02-1.2 percent of EOs. We also found that all EOs inhibit egg hatching. Thus, EOs can mediate both rapid and long-term anthelmintic effects. We determined that trans-cinnamaldehyde (TC), a major component of C. verum EO, produces both paralysis and egg-hatching inhibition. By testing mutant worms, we identified that muscle L-AChR and GABA receptors are EO and TC targets in vivo. Electrophysiological studies from C. elegans cultured muscle cells identified the mechanism underlying the antiparasitic effect. Thus, by modulating two receptors with key roles in worm motility, these EO emerge as novel sources of anthelmintic compounds.