Model for the Action of Tetrodotoxin and Batrachotoxin

Abstract

IT has been suggested^1–3 that the ionic permeability of membranes is controlled by complex formation on the surface between various phosphorylated nucleosides and protein chains. This is based on the fact that guanine, cytidine and adenine are complementary to glutamate, arginine, and glutamine respectively and all four bases are complementary to glutamine. Adenosine triphosphate (ATP) has been reported to bind strongly to rat brain synaptosomal protein—probably to glutamine moieties⁴. It is postulated that complex formation is promoted by prostaglandins and disrupted by transmitters and on this basis it has been possible to suggest working molecular specifications for acetylcholine (ACh), γ-aminobutyric acid (GABA) and glutamate receptors based on guanine–glutamate and cytidine–arginine pairs, and for prostaglandin and catecholamine action based largely on the adenine–glutamine pairs. This hypothesis has explained a quantity of structure-activity relationship data on agonists and antagonists of these compounds as detailed in refs. 1–3.