6-Bromohypaphorine from Marine Nudibranch Mollusk Hermissenda crassicornis is an Agonist of Human α7 Nicotinic Acetylcholine Receptor

6-Bromohypaphorine (6-BHP) has been isolated from the marine sponges Pachymatisma johnstoni, Aplysina sp., and the tunicate Aplidium conicum, but data on its biological activity were not available. For the nudibranch mollusk Hermissenda crassicornis no endogenous compounds were known, and here we de...

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Main Authors: Igor E. Kasheverov, Irina V. Shelukhina, Denis S. Kudryavtsev, Tatyana N. Makarieva, Ekaterina N. Spirova, Alla G. Guzii, Valentin A. Stonik, Victor I. Tsetlin
Format: Article
Language:English
Published: MDPI AG 2015-03-01
Series:Marine Drugs
Subjects:
Online Access:http://www.mdpi.com/1660-3397/13/3/1255
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author Igor E. Kasheverov
Irina V. Shelukhina
Denis S. Kudryavtsev
Tatyana N. Makarieva
Ekaterina N. Spirova
Alla G. Guzii
Valentin A. Stonik
Victor I. Tsetlin
author_facet Igor E. Kasheverov
Irina V. Shelukhina
Denis S. Kudryavtsev
Tatyana N. Makarieva
Ekaterina N. Spirova
Alla G. Guzii
Valentin A. Stonik
Victor I. Tsetlin
author_sort Igor E. Kasheverov
collection DOAJ
description 6-Bromohypaphorine (6-BHP) has been isolated from the marine sponges Pachymatisma johnstoni, Aplysina sp., and the tunicate Aplidium conicum, but data on its biological activity were not available. For the nudibranch mollusk Hermissenda crassicornis no endogenous compounds were known, and here we describe the isolation of 6-BHP from this mollusk and its effects on different nicotinic acetylcholine receptors (nAChR). Two-electrode voltage-clamp experiments on the chimeric α7 nAChR (built of chicken α7 ligand-binding and glycine receptor transmembrane domains) or on rat α4β2 nAChR expressed in Xenopus oocytes revealed no action of 6-BHP. However, in radioligand analysis, 6-BHP competed with radioiodinated α-bungarotoxin for binding to human α7 nAChR expressed in GH4C1 cells (IC50 23 ± 1 μM), but showed no competition on muscle-type nAChR from Torpedo californica. In Ca2+-imaging experiments on the human α7 nAChR expressed in the Neuro2a cells, 6-BHP in the presence of PNU120596 behaved as an agonist (EC50 ~80 μM). To the best of our knowledge, 6-BHP is the first low-molecular weight compound from marine source which is an agonist of the nAChR subtype. This may have physiological importance because H. crassicornis, with its simple and tractable nervous system, is a convenient model system for studying the learning and memory processes.
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spelling doaj.art-17e2cedd82fe4bd895b643523d0053f42022-12-22T01:59:18ZengMDPI AGMarine Drugs1660-33972015-03-011331255126610.3390/md13031255md130312556-Bromohypaphorine from Marine Nudibranch Mollusk Hermissenda crassicornis is an Agonist of Human α7 Nicotinic Acetylcholine ReceptorIgor E. Kasheverov0Irina V. Shelukhina1Denis S. Kudryavtsev2Tatyana N. Makarieva3Ekaterina N. Spirova4Alla G. Guzii5Valentin A. Stonik6Victor I. Tsetlin7Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya Street, 16/10, Moscow 117997, RussiaShemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya Street, 16/10, Moscow 117997, RussiaShemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya Street, 16/10, Moscow 117997, RussiaElyakov Pacific Institute of Bioorganic Chemistry (PIBOC), Russian Academy of Sciences, Prospect 100 let Vladivostoku, 159, Vladivostok 690022, RussiaShemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya Street, 16/10, Moscow 117997, RussiaElyakov Pacific Institute of Bioorganic Chemistry (PIBOC), Russian Academy of Sciences, Prospect 100 let Vladivostoku, 159, Vladivostok 690022, RussiaElyakov Pacific Institute of Bioorganic Chemistry (PIBOC), Russian Academy of Sciences, Prospect 100 let Vladivostoku, 159, Vladivostok 690022, RussiaShemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya Street, 16/10, Moscow 117997, Russia6-Bromohypaphorine (6-BHP) has been isolated from the marine sponges Pachymatisma johnstoni, Aplysina sp., and the tunicate Aplidium conicum, but data on its biological activity were not available. For the nudibranch mollusk Hermissenda crassicornis no endogenous compounds were known, and here we describe the isolation of 6-BHP from this mollusk and its effects on different nicotinic acetylcholine receptors (nAChR). Two-electrode voltage-clamp experiments on the chimeric α7 nAChR (built of chicken α7 ligand-binding and glycine receptor transmembrane domains) or on rat α4β2 nAChR expressed in Xenopus oocytes revealed no action of 6-BHP. However, in radioligand analysis, 6-BHP competed with radioiodinated α-bungarotoxin for binding to human α7 nAChR expressed in GH4C1 cells (IC50 23 ± 1 μM), but showed no competition on muscle-type nAChR from Torpedo californica. In Ca2+-imaging experiments on the human α7 nAChR expressed in the Neuro2a cells, 6-BHP in the presence of PNU120596 behaved as an agonist (EC50 ~80 μM). To the best of our knowledge, 6-BHP is the first low-molecular weight compound from marine source which is an agonist of the nAChR subtype. This may have physiological importance because H. crassicornis, with its simple and tractable nervous system, is a convenient model system for studying the learning and memory processes.http://www.mdpi.com/1660-3397/13/3/12556-bromohypaphorinenicotinic acetylcholine receptorsagonist
spellingShingle Igor E. Kasheverov
Irina V. Shelukhina
Denis S. Kudryavtsev
Tatyana N. Makarieva
Ekaterina N. Spirova
Alla G. Guzii
Valentin A. Stonik
Victor I. Tsetlin
6-Bromohypaphorine from Marine Nudibranch Mollusk Hermissenda crassicornis is an Agonist of Human α7 Nicotinic Acetylcholine Receptor
Marine Drugs
6-bromohypaphorine
nicotinic acetylcholine receptors
agonist
title 6-Bromohypaphorine from Marine Nudibranch Mollusk Hermissenda crassicornis is an Agonist of Human α7 Nicotinic Acetylcholine Receptor
title_full 6-Bromohypaphorine from Marine Nudibranch Mollusk Hermissenda crassicornis is an Agonist of Human α7 Nicotinic Acetylcholine Receptor
title_fullStr 6-Bromohypaphorine from Marine Nudibranch Mollusk Hermissenda crassicornis is an Agonist of Human α7 Nicotinic Acetylcholine Receptor
title_full_unstemmed 6-Bromohypaphorine from Marine Nudibranch Mollusk Hermissenda crassicornis is an Agonist of Human α7 Nicotinic Acetylcholine Receptor
title_short 6-Bromohypaphorine from Marine Nudibranch Mollusk Hermissenda crassicornis is an Agonist of Human α7 Nicotinic Acetylcholine Receptor
title_sort 6 bromohypaphorine from marine nudibranch mollusk hermissenda crassicornis is an agonist of human α7 nicotinic acetylcholine receptor
topic 6-bromohypaphorine
nicotinic acetylcholine receptors
agonist
url http://www.mdpi.com/1660-3397/13/3/1255
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