Inhibition of agrin-induced acetylcholine-receptor aggregation by heparin, heparan sulfate, and other polyanions.
Heparin and heparan sulfate have been shown to block nerve-induced acetylcholine-receptor (AChR) aggregation at developing neuromuscular junctions. We found that heparin, heparan sulfate, and a wide variety of other polyanions also inhibited agrin-induced AChR aggregation. The more highly charged the polyanion, the more potent it was as an inhibitor. Inhibition of agrin-induced AChR aggregation was due, at least in part, to the formation of a complex between the polyanion and agrin that was inactive. These findings are consistent with the hypothesis that nerve-induced aggregation of AChRs is mediated by the release of agrin, or a closely related protein, from axon terminals and suggest that a polyanion, such as a sulfated proteoglycan, may be involved in the interaction of agrin with its receptor on the myotube surface.
Department of Neurobiology, Stanford University School of Medicine, California 94305.
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Wallace
D018171:Agrin; D000818:Animals; D002642:Chick Embryo; D002809:Chondroitin Sulfates / Q000494:pharmacology; D016264:Dextran Sulfate / Q000494:pharmacology; D003911:Dextrans / Q000494:pharmacology; D004557:Electric Organ / Q000737:chemistry; D006493:Heparin / Q000494:pharmacology*; D006497:Heparan Sulfate / Q000494:pharmacology*; D007700:Kinetics; D009419:Nerve Tissue Proteins / Q000302:isolation & purification / Q000494:pharmacology*; D010455:Peptides / Q000494:pharmacology; D011134:Polysaccharides / Q000494:pharmacology; D011950:Receptors, Cholinergic / Q000187:drug effects / Q000502:physiology*; D014101:Torpedo
D018171:Agrin; D002809:Chondroitin Sulfates; D016264:Dextran Sulfate; D003911:Dextrans; D006493:Heparin; D006497:Heparan Sulfate; D009419:Nerve Tissue Proteins; D010455:Peptides; D011134:Polysaccharides; D011950:Receptors, Cholinergic; C017645:polyaspartate; C007789:fucoidan