Toxin receptor studies 77-77 complexation

Thus three lines of evidence define the rapidly dissociating receptor as the LR complex. Conditions known to uncouple R from G--first, guanine nucleotide and second, pertussis toxin—produce LR third, reconstitution of G protein restores receptor affinity, sensitivity to guanine nucleotide, and effector activation. In this sense, the ligand and binding behavior of this system is analogous to that of the beta-adrenergic receptor, where the LR and LRG complexes have already been studied with purified proteins and reconstituted membrane preparations (2,i0). 

Research in this area advanced in the 1970 s as several groups reported the isolation of potent toxins from P. brevis cell cultures (2-7). To date, the structures of at least eight active neurotoxins have been elucidated (PbTx-1 through PbTx-8) (8). Early studies of toxic fractions indicated diverse pathophysiological effects in vivo as well as in a number of nerve and muscle tissue preparations (reviewed in 9-11). The site of action of two major brevetoxins, PbTx-2 and PbTx-3, has been shown to be the voltage-sensitive sodium channel (8,12). These compounds bind to a specific receptor site on the channel complex where they cause persistent activation, increased Na flux, and subsequent depolarization of excitable cells at resting... 

The metabolism of GSLs has been studied in cultured human fibroblasts from normal subjects, patients with lipid storage diseases, and those with FH. The content of the GSLs, as well as activities of the biosynthetic enzymes, the glycosyltransferases and the lysosomal GSL hydrolases,have been studied. Complex gangliosides, such as M1, GDla, have been found in this cell system to serve as receptors for cholera toxin and thyrotropin, respectively (24-26). More recently, GT1 and GDla have been postulated to be receptors for fibronectin in cultured fibroblasts... 

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