Modification of glomerular basement membrane following the administration of the lathyrogen aminoacetonitrile to rats.

Lathyrogens are a group of compounds which on ingestion induce a disease known as lathyrism [ 11. The administration of /?-aminopropionitrile, or its homolague, aminoacetonitrile, to laboratory animals results in osteolathyrism. Both these lathyrogens inhibit the activity of lysyl oxidase an enzyme important in the post-translational formation of inter- and intramolecular collagen crosslinks [ 21. Glomerular basement membrane (GBM) is a member of the collagen family and contains collagen-like and polar regions [3]. When GBM is solubilised in sodium dodecyl sulphate (SDS) and 2-mercaptoethanol a residue, accounting for 20% of the total protein of the membrane, remains. Amino acid analysis demonstrated that the residue was collagenous and contained high amounts of glycine, hydroxyproline and hydroxylysine, while the material solubilised from the membrane contamed a greater proportion of polar amino acids [4]. Glomerular nephropathies have been reported in patients with rheumatoid arthritis who were treated with D-penicillamine [ 51. This drug, like aminoacetonitrile, interferes with collagen crosslinks [6] although it has a different mechanism of action [7]. It was of interest to determine whether aminoacetonitrile had an effect on the solubility and composition of GBM. Osteolathyrism was produced in rats by feeding aminoacetonitrile and its effect on rats of different ages compared. The ammo acid composition, solubility and subunit pattern of GBM isolated from these rats is reported.