FUNCTIONAL-ROLE FOR GLYCOSYLATED SUBTYPES OF RAT ENDOTHELIN RECEPTORS

Glycosylation of endothelin (ET) receptors was found to occur in rat c erebellar and atrial membranes. Specifically, we investigated whether the ETA and ETB receptor subtypes differed in their sensitivity to deg lycosylation treatment and whether the two affinity states (nanomolar and picomolar) observed in each receptor subtype reflect differences i n glycosylation states. Pretreatment of cerebellar or atrial membranes with endoglycosidase H (endo H) caused a marked decrease in the numbe r of maximal binding sites that bind ligand with nanomolar affinity, w hereas ligand affinity remained the same. The picomolar-affinity bindi ng sites were not affected by endo H. The use of specific antagonists indicated that the receptor subtype most likely to be influenced by gl ycosylation is ETA. We suggest that in both cerebellar and atrial memb ranes, the carbohydrate chains of the ETA receptor contribute to the b inding of ligand to the nanomolar affinity binding sites, but not to t he picomolar-affinity binding sites. (C) 1998 Academic Press.