Defining modulatory inputs into CNS neuronal subclasses by functional pharmacological profiling.

Previously we defined neuronal subclasses within the mouse peripheral nervous system using an experimental strategy called "constellation pharmacology." Here we demonstrate the broad applicability of constellation pharmacology by extending it to the CNS and specifically to the ventral respiratory column (VRC) of mouse brainstem, a region containing the neuronal network controlling respiratory rhythm. Analysis of dissociated cells from this locus revealed three major cell classes, each encompassing multiple subclasses.

From molecular phylogeny towards differentiating pharmacology for NMDA receptor subtypes.

In order to decode the roles that N-methyl-D-aspartate (NMDA) receptors play in excitatory neurotransmission, synaptic plasticity, and neuropathologies, there is need for ligands that differ in their subtype selectivity. The conantokin family of Conus peptides is the only group of peptidic natural products known to target NMDA receptors. Using a search that was guided by phylogeny, we identified new conantokins from the marine snail Conus bocki that complement the current repertoire of NMDA receptor pharmacology.

Characterization of conantokin Rl-A: molecular phylogeny as structure/function study.

A multidisciplinary strategy for discovery of new Conus venom peptides combines molecular genetics and phylogenetics with peptide chemistry and neuropharmacology. Here we describe application of this approach to the conantokin family of conopeptides targeting NMDA receptors. A new conantokin from Conus rolani, ConRl-A, was identified using molecular phylogeny and subsequently synthesized and functionally characterized.

Neuroprotective and cardioprotective conopeptides: an emerging class of drug leads.

The peptides in the venoms of predatory marine snails belonging to the genus Conus ('cone snails') have well-established therapeutic applications for the treatment of pain and epilepsy. This review discusses the neuroprotective and cardioprotective potential of four families of Conus peptides (conopeptides), including omega-conotoxins that target voltage-gated Ca2+ channels, conantokins that target NMDA receptors, mu-conotoxins that target voltage-gated Na+ channels, and kappa- and kappaM-conotoxins that target K+ channels. The diversity of Conus peptides that have already been shown to exhibit neuroprotective/cardioprotective activity suggests that marine snail venoms are a potentially rich source of drug leads with diverse mechanisms.

Conantokin-Br from Conus brettinghami and selectivity determinants for the NR2D subunit of the NMDA receptor.

Conantokins are venom peptides from marine cone snails that are NMDA receptor antagonists. Here, we report the characterization of a 24 AA conantokin from Conus brettinghami Coomans , H. E.