Parazoanthoxanthin A blocks Torpedo nicotinic acetylcholine receptors.
Nicotinic acetylcholine receptors are implicated in different nervous system-related disorders, and their modulation could improve existing therapy of these diseases. Parazoanthoxanthin A (ParaA) is a fluorescent pigment of the group of zoanthoxanthins. Since it is a potent acetylcholinesterase inhibitor, it may also bind to nicotinic acetylcholine receptors (nAChRs). For this reason its effect on Torpedo nAChR (alpha1(2)betagammadelta) transplanted to Xenopus laevis oocytes was evaluated, using the voltage-clamp technique. ParaA dose-dependently reduced the acetylcholine-induced currents. This effect was fully reversible only at lower concentrations. ParaA also reduced the Hill coefficient and the time to peak current, indicating a channel blocking mode of action. On the other hand, the combined effect of ParaA and d-tubocurarine (d-TC) on acetylcholine-induced currents exhibited only partial additivity, assuming a competitive mode of action of ParaA on nAChR. These results indicate a dual mode of action of ParaA on the Torpedo AChR.
Rozman
Klara Bulc
KB
Institute of Pathophysiology, Faculty of Medicine, University of Ljubljana, Zaloska cesta 4, 1000 Ljubljana, Slovenia. klara.bulc@rozman.si
Araoz
Romulo
R
Sepcić
Kristina
K
Molgo
Jordi
J
Suput
Dusan
D
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D003508:Cycloheptanes / Q000494:pharmacology*; D004553:Electric Conductivity; D009132:Muscles / Q000378:metabolism; D018733:Nicotinic Antagonists / Q000494:pharmacology*; D009865:Oocytes / Q000378:metabolism; D018408:Patch-Clamp Techniques; D011978:Receptors, Nicotinic / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D014101:Torpedo; D014403:Tubocurarine / Q000494:pharmacology; D014982:Xenopus laevis / Q000235:genetics
D003508:Cycloheptanes; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; C114237:parazoanthoxanthin A; D000109:Acetylcholine; D014403:Tubocurarine