ISSN:
1527-3458
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
Calcium channels are represented by at least 9 distinct genes (calcium channel classes A-I), corresponding to at least 5 functional and pharmacological “types” (L, N, P/Q, R and T). Selective L-, N-, and T-type channel antagonists are either in clinical use or in late stage clinical trials, while antagonists of P/Q channels are known to be toxic. No selective ligand has been identified for the R-type (class E), and its function and pharmacology are consequently, poorly understood. We review recent work on the discovery and initial characterization of SNX-482, the first known selective antagonist of R-type calcium channels. SNX-482 is a 41 residue acidic peptide with three disulfide bonds that has been isolated from the venom of the African tarantula, Hysterocrates gigas. In cell-based assays, it is a potent and selective inhibitor of the class E or R-type calcium channel. SNX-482 blocks some but not all native R-type currents: it blocks an R-type current in vertebrate neurohypophysis, but it does not block an R-type current in cerebellar granule cells. The peptide blocks oxytocin but not vasopressin release, suggesting a possible utility for SNX-482 as a neuroendocrine modulator. The peptide possesses antiseizure activity in several animal models of epilepsy, suggesting that class E antagonists may have pharmacological use in seizure disorders.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1111/j.1527-3458.2000.tb00143.x
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