title: Inhibition of nicotinic acetylcholine receptors, a novel facet in the pleiotropic activities of snake venom phospholipases A2.
abstract: Phospholipases A2 represent the most abundant family of snake venom proteins. They manifest an array of biological activities, which is constantly expanding. We have recently shown that a protein bitanarin, isolated from the venom of the puff adder Bitis arietans and possessing high phospholipolytic activity, interacts with different types of nicotinic acetylcholine receptors and with the acetylcholine-binding protein. To check if this property is characteristic to all venom phospholipases A2, we have studied the capability of these enzymes from other snakes to block the responses of Lymnaea stagnalis neurons to acetylcholine or cytisine and to inhibit α-bungarotoxin binding to nicotinic acetylcholine receptors and acetylcholine-binding proteins. Here we present the evidence that phospholipases A2 from venoms of vipers Vipera ursinii and V. nikolskii, cobra Naja kaouthia, and krait Bungarus fasciatus from different snake families suppress the acetylcholine- or cytisine-elicited currents in L. stagnalis neurons and compete with α-bungarotoxin for binding to muscle- and neuronal α7-types of nicotinic acetylcholine receptor, as well as to acetylcholine-binding proteins. As the phospholipase A2 content in venoms is quite high, under some conditions the activity found may contribute to the deleterious venom effects. The results obtained suggest that the ability to interact with nicotinic acetylcholine receptors may be a general property of snake venom phospholipases A2, which add a new target to the numerous activities of these enzymes.
authors.affiliation: Institute of Cell Biophysics, Russian Academy of Sciences, Ul. Institutskaya 3, Pushchino, Moscow Region 142290, Russia.
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Vulfius
authors.affiliation: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Ul. Miklukho-Maklaya 16/10, Moscow 117997, Russia.
authors.forename: Igor E
authors.initials: IE
authors.lastname: Kasheverov
authors.affiliation: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Ul. Miklukho-Maklaya 16/10, Moscow 117997, Russia.
authors.forename: Vladislav G
authors.initials: VG
authors.lastname: Starkov
authors.affiliation: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Ul. Miklukho-Maklaya 16/10, Moscow 117997, Russia.
authors.forename: Alexey V
authors.initials: AV
authors.lastname: Osipov
authors.affiliation: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Ul. Miklukho-Maklaya 16/10, Moscow 117997, Russia.
authors.forename: Tatyana V
authors.initials: TV
authors.lastname: Andreeva
authors.affiliation: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Ul. Miklukho-Maklaya 16/10, Moscow 117997, Russia.
authors.forename: Sergey Yu
authors.initials: SY
authors.lastname: Filkin
authors.affiliation: Institute of Cell Biophysics, Russian Academy of Sciences, Ul. Institutskaya 3, Pushchino, Moscow Region 142290, Russia.
authors.forename: Elena V
authors.initials: EV
authors.lastname: Gorbacheva
authors.affiliation: Institute of Cell Biophysics, Russian Academy of Sciences, Ul. Institutskaya 3, Pushchino, Moscow Region 142290, Russia.
authors.forename: Maxim E
authors.initials: ME
authors.lastname: Astashev
authors.affiliation: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Ul. Miklukho-Maklaya 16/10, Moscow 117997, Russia.
authors.forename: Victor I
authors.initials: VI
authors.lastname: Tsetlin
authors.affiliation: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Ul. Miklukho-Maklaya 16/10, Moscow 117997, Russia.
authors.forename: Yuri N
authors.initials: YN
authors.lastname: Utkin
mesh_terms: D000200:Action Potentials; D000595:Amino Acid Sequence; D000818:Animals; D008195:Lymnaea; D008969:Molecular Sequence Data; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D018733:Nicotinic Antagonists / Q000737:chemistry / Q000494:pharmacology*; D054467:Phospholipases A2 / Q000494:pharmacology*; D011485:Protein Binding; D011978:Receptors, Nicotinic / Q000737:chemistry / Q000378:metabolism; D012910:Snake Venoms / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; D012910:Snake Venoms; D054467:Phospholipases A2