Pharmacological families

Conotoxins, the disulfide rich conopeptides, are classified according to three schemes: the similarities between the ER signal sequence of the conotoxin precursors (gene superfamilies), the cysteine patterns of conotoxin mature peptide regions (cysteine frameworks), and the specificities to pharmacological targets (pharmacological families). This page provides a brief introduction to the pharmacological families and a list of the pharmacological families used in ConoServer. The two other classification schemes are detailed in separate pages accessible from the menu on the left. A more comprehensive discussion of the conopeptide classification schemes can be found in Kaas et al. Toxicon 2010 [1].

Pharmacological families are defined in ConoServer as conopeptides sharing the same receptor specificities, which include the type of targeted receptors and the physiological activity (agonist, antagonist and other physiologically measurable characteristics). The pharmacological families are noted using a greek letter.

Some differences exist between the nomenclature used for pharmacological families in the literature and in ConoServer. For example, the information regarding binding sites are not included in the definition used in ConoServer, and therefore the αA family used in the literature is included in the α pharmacological family in ConoServer. Information on the binding sites are difficult to obtain and are here considered as inadequate for a general classification of conopeptide pharmacological effects. Binding site informations are indicated as notes in ConoServer. Differences between the literature and ConoServer definitions only concern a small number of peptides, as detailed in Kaas et al. Toxicon 2010 [1].

Table 1: Pharmacological families used in ConoServer. This table is automatically generated and therefore kept up-to-date with the content of ConoServer.
Family Definition Representative
α (alpha) Nicotinic acetylcholine receptors (nAChR) GI Gray,W.R. et al. (1981) J. Biol. Chem. 256:4734-4740
γ (gamma) Neuronal pacemaker cation currents (inward cation current) PnVIIA, TxVIIA Fainzilber,M. et al. (1998) Biochemistry 37:1470-1477
δ (delta) Voltage-gated Na channels (agonist, delay inactivation) TxVIA Fainzilber,M. et al. (1991) Eur. J. Biochem. 202:589-595
ε (epsilon) Presynaptic Ca channels or G protein-coupled presynaptic receptors TxVA Rigby,A.C. et al. (1999) Proc. Natl. Acad. Sci. U.S.A. 96:5758-5763
ι (iota) Voltage-gated Na channels (agonist, no delayed inactivation) RXIA Buczek,O. et al. (2007) Biochemistry 46:9929-9940
κ (kappa) Voltage-gated K channels (blocker) PVIIA Terlau,H. et al. (1996) Nature 381:148-151
μ (mu) Voltage-gated Na channels (antagonist, blocker) GIIIA Cruz,L.J. et al. (1985) J. Biol. Chem. 260:9280-9288
ρ (rho) Alpha1-adrenoceptors (GPCR) TIA Sharpe,I.A. et al. (2001) Nat. Neurosci. 4:902-907
σ (sigma) Serotonin-gated ion channels 5-HT3 GVIIIA England,L.J. et al. (1998) Science 281:575-578
τ (tau) Somatostatin receptor CnVA Petrel,C. et al. (2013) Biochem. Pharmacol.
χ (chi) Neuronal noradrenaline transporter MrIA, CMrVIA Sharpe,I.A. et al. (2001) Nat. Neurosci. 4:902-907
ω (omega) Voltage-gated Ca channels (blocker) GVIA Kerr,L.M. and Yoshikami,D. (1984) Nature 308:282-284

[1]Kaas,Q. et al. (2010) Toxicon 55:1491-1509