Evaluation of the role of the asialoglycoprotein receptor in the clearance of UK-279,276 (recombinant neutrophil inhibitory factor).
1. UK-279,276 or recombinant neutrophil inhibitory factor (rNIF) is a glycoprotein that has been investigated as an intravenous treatment for stroke. Previous data indicate that the asialoglycoprotein receptor (ASGPR) in the liver might have a role in the uptake and clearance of UK-279,276 from plasma in rats and dogs. 2. Biliary elimination of sialo UK-279,276 can be inhibited by the co-administration of asialo fetuin, a known substrate for ASGPR. These data are in keeping with sialo UK-279,276 being cleared by ASGPR. 3. In vitro experiments have demonstrated that asialo UK-279,276 (Sialo UK-279,276 treated to remove the sialic acid residues present on the glycans) shows a significantly greater uptake in rat, dog and human precision-cut liver slices than the sialylated protein. The addition of asialo fetuin to precision-cut liver slice incubations (rat, dog and man) containing asialo UK-279,276 reduced the uptake to levels similar to those seen for the sialylated protein. These data support the potential role of the ASGPR in the clearance of UK-279,276 in rat, dog and man.
D000818:Animals; D037263:Asialoglycoprotein Receptor / Q000378:metabolism*; D001646:Bile / Q000378:metabolism; D001652:Bile Ducts / Q000378:metabolism; D004285:Dogs; D016650:Fluorescein-5-isothiocyanate; D005456:Fluorescent Dyes; D006023:Glycoproteins / Q000493:pharmacokinetics*; D015801:Helminth Proteins / Q000493:pharmacokinetics*; D006801:Humans; D066298:In Vitro Techniques; D008099:Liver / Q000033:anatomy & histology / Q000166:cytology / Q000378:metabolism; D008565:Membrane Proteins / Q000493:pharmacokinetics*; D051381:Rats; D011916:Rats, Inbred F344; D011994:Recombinant Proteins / Q000493:pharmacokinetics; D013045:Species Specificity
D037263:Asialoglycoprotein Receptor; D005456:Fluorescent Dyes; D006023:Glycoproteins; D015801:Helminth Proteins; D008565:Membrane Proteins; D011994:Recombinant Proteins; C476006:UK279276; C086581:NIF protein, Ancylostoma caninum; D016650:Fluorescein-5-isothiocyanate