TRPV1 activation power can switch an action mode for its polypeptide ligands.
| Autor: | Nikolaev MV; I.M.Sechenov Institute of Evolutionary Physiology and Biochemistry RAS, St.Petersburg, Russia., Dorofeeva NA; I.M.Sechenov Institute of Evolutionary Physiology and Biochemistry RAS, St.Petersburg, Russia., Komarova MS; I.M.Sechenov Institute of Evolutionary Physiology and Biochemistry RAS, St.Petersburg, Russia., Korolkova YV; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, RAS, Moscow, Russia., Andreev YA; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, RAS, Moscow, Russia.; Sechenov First Moscow State Medical University, Institute of Molecular Medicine, Moscow, Russia., Mosharova IV; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, RAS, Moscow, Russia., Grishin EV; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, RAS, Moscow, Russia., Tikhonov DB; I.M.Sechenov Institute of Evolutionary Physiology and Biochemistry RAS, St.Petersburg, Russia., Kozlov SA; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, RAS, Moscow, Russia. |
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| Jazyk: | angličtina |
| Zdroj: | PloS one [PLoS One] 2017 May 05; Vol. 12 (5), pp. e0177077. Date of Electronic Publication: 2017 May 05 (Print Publication: 2017). |
| DOI: | 10.1371/journal.pone.0177077 |
| Abstrakt: | TRPV1 (vanilloid) receptors are activated by different types of stimuli including capsaicin, acidification and heat. Various ligands demonstrate stimulus-dependent action on TRPV1. In the present work we studied the action of polypeptides isolated from sea anemone Heteractis crispa (APHC1, APHC2 and APHC3) on rat TRPV1 receptors stably expressed in CHO cells using electrophysiological recordings, fluorescent Ca2+ measurements and molecular modeling. The APHCs potentiated TRPV1 responses to low (3-300 nM) concentrations of capsaicin but inhibited responses to high (>3.0 μM) concentrations. The activity-dependent action was also found for TRPV1 responses to 2APB and acidification. Thus the action mode of APHCs is bimodal and depended on the activation stimuli strength-potentiation of low-amplitude responses and no effect/inhibition of high-amplitude responses. The double-gate model of TRPV1 activation suggests that APHC-polypeptides may stabilize an intermediate state during the receptor activation. Molecular modeling revealed putative binding site at the outer loops of TRPV1. Binding to this site can directly affect activation by protons and can be allosterically coupled with capsaicin site. The results are important for further investigations of both TRPV1 and its ligands for potential therapeutic use. |
| Databáze: | MEDLINE |
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