These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: [Kinetics of receptor-mediated endocytosis of polypeptide hormones that governs the overall hormone disposition in the body: analysis of the uptake process of epidermal growth factor by the liver and kidney].
    Author: Sugiyama Y.
    Journal: Yakugaku Zasshi; 1991 Dec; 111(12):709-36. PubMed ID: 1806655.
    Abstract:
    A remarkable feature of the disposition of polypeptide hormones and their analogues is the contribution of specific binding sites (receptors) to the polypeptides distribution and clearance in the body. The concept of "clearance receptor" is now well established, and receptor-mediated endocytosis (RME) is known as a general mechanism in the uptake of biologically important polypeptides. This review article focuses on the kinetic analysis of the RME of epidermal growth factor (EGF) based mainly on our observations of EGF handling by the liver and kidney. Pharmacokinetic analysis of the tissue distribution of EGF in rats performed in vivo clarified that the uptake of EGF by the liver and kidney exhibited clear saturation with Km values of 7 nM and 0.4 nM, respectively, and that both tissues could account for more than 80% of the total plasma clearance of EGF in the distribution phase. The hepatic and renal handlings of EGF by isolated perfused organs were also analyzed to obtain the kinetic parameters with respect to RME. In the overall RME process in the liver, the EGF-receptor association and dissociation processes are rapid (mean time less than 1 min), the degradation process is much slower (mean time 4-5 h) and the internalization process is intermediate (mean time 4-5 min). The mean time required for the recovery of receptors after being down-regulated in the liver is approximately 30 min, and was much shorter than those in other tissues. Such rapid recovery from the receptor down regulation in the liver reflects the process of recycling of internalized EGF receptors to the cell surface. The kinetic parameters obtained from the perfused livers and from isolated hepatocytes were compared, and a significant difference was observed only for the association rate constant (kon). A hypothesis accounting for this difference is proposed, in which the association rate of EGF to the cell surface receptor is considered to be limited by the diffusion in the unstirred water layer in the interstitial space of the intact liver such as the perfused liver. The comparison of EGF handling between the filtering and nonfiltering perfused kidneys demonstrated that the bulk of receptor-mediated EGF uptake takes place via the antiluminal plasma membrane with very high affinity (Kd = 0.1 nM).
    [Abstract] [Full Text] [Related] [New Search]