title: 6-bromohypaphorine from marine nudibranch mollusk Hermissenda crassicornis is an agonist of human α7 nicotinic acetylcholine receptor.
abstract: 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.
authors.affiliation: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya Street, 16/10, Moscow 117997, Russia. iekash@mx.ibch.ru.
authors.forename: Igor E
authors.initials: IE
authors.lastname: Kasheverov
authors.affiliation: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya Street, 16/10, Moscow 117997, Russia. ner-neri@mail.ru.
authors.forename: Irina V
authors.initials: IV
authors.lastname: Shelukhina
authors.affiliation: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya Street, 16/10, Moscow 117997, Russia. kudryavtsev@ibch.ru.
authors.forename: Denis S
authors.initials: DS
authors.lastname: Kudryavtsev
authors.affiliation: Elyakov Pacific Institute of Bioorganic Chemistry (PIBOC), Russian Academy of Sciences, Prospect 100 let Vladivostoku, 159, Vladivostok 690022, Russia. makarieva@piboc.dvo.ru.
authors.forename: Tatyana N
authors.initials: TN
authors.lastname: Makarieva
authors.affiliation: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya Street, 16/10, Moscow 117997, Russia. katya_spirova@mail.ru.
authors.forename: Ekaterina N
authors.initials: EN
authors.lastname: Spirova
authors.affiliation: Elyakov Pacific Institute of Bioorganic Chemistry (PIBOC), Russian Academy of Sciences, Prospect 100 let Vladivostoku, 159, Vladivostok 690022, Russia. gagry@rambler.ru.
authors.forename: Alla G
authors.initials: AG
authors.lastname: Guzii
authors.affiliation: Elyakov Pacific Institute of Bioorganic Chemistry (PIBOC), Russian Academy of Sciences, Prospect 100 let Vladivostoku, 159, Vladivostok 690022, Russia. stonik@piboc.dvo.ru.
authors.forename: Valentin A
authors.initials: VA
authors.lastname: Stonik
authors.affiliation: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya Street, 16/10, Moscow 117997, Russia. vits@mx.ibch.ru.
authors.forename: Victor I
authors.initials: VI
authors.lastname: Tsetlin
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D002645:Chickens; D049870:Hermissenda / Q000378:metabolism*; D006801:Humans; D020128:Inhibitory Concentration 50; D008970:Molecular Weight; D018722:Nicotinic Agonists / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D009865:Oocytes; D018408:Patch-Clamp Techniques; D051381:Rats; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000378:metabolism; D013045:Species Specificity; D014101:Torpedo; D014364:Tryptophan / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000494:pharmacology; D014982:Xenopus laevis; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000819:agonists*
chemical_list: D018722:Nicotinic Agonists; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; C403531:nicotinic receptor alpha4beta2; C014372:L-6-bromohypaporphine; D014364:Tryptophan