Analgesic Pharmacology And Target Of Conotoxin LvD2

The cone snails belong to the genus Conus, are carnivorous molluscs, comprising700different species, all of which capture prey by injecting a peptide-rich venom. It has been estimated that the venom of a single Conus species may contain between1000-1900different toxin components. Thus, the total number of conotoxins among the entire genus may consist of over50,0000distinct neurologically active peptides.These conotoxins are small size,(8-30aa), cys-rich and exhibit an unprecedented degree of post-translational modification.These small conopeptides can be generally classified into two major categories:those in the majority with disulfide bonds; those in the minority with a single or no disulfide bond. Acording to characteristic cysteine arrangement and a highly conserved signal sequence in the precursors, conotoxins can be divided into some superfamily:O-, M-, A-, S-, T-, P-, I-. The superfamily may be subdivided into several families with distinct pharmacological activities. For example A-superfamily(a-, aA-, kA-and p-conotoxins); M-superfamily(μ-and Ψ-conotoxins); O-superfamily (ω-, μO,δ-, and K-conotoxins); T-superfamily (τ-and x-conotoxins) and so on.The individual peptides in a conotoxin family are typically each selectively targeted to a diverse set of different molecular isoforms within the same ion channel family. These days,A variety of conopeptides have been identified to target voltage-gated potassium channels as well as G protein-linked receptors. Thus, conopeptides have attracted extensive attention with their potentials to be developed as new research tools in neuroscience and as novel medications.The main objective of this research is to test analgesic activity of the new conotoxins LvD2in animal pain models and to identify its receptor targets. Firstly, Three physiological analgesic model, including hotplate test, tail flick test and formalin test were employed to test analgesic effect of conotoxin LvD2via injection of intracerebroventricular injection (i.c.v.), intraperitoneal injection (i.p) and intrathecal injection (i.v.). Secondly, We also investigated the effects of LvD2in a rat chronic constriction injury (CCI) model which are generally used as neuropathic pain model. Lastly, we expressed different kinds of acetylcholine receptor subunits in Xenopus Laevis Oocytes to characterize binding receptors of LvD2. Results: conotoxin LvD2showed significant analgesic effects on different pain models through various administration methods. At the same time, the results indicated that LvD2selectively inhibited alpha3beta2and alpha3beta4nicotinic acetylcholine receptors.