High affinity peptide histidine isoleucine-preferring receptors in rat liver.
Peptide Histidine Isoleucine (PHI) is generally considered a low affinity agonist for Vasoactive Intestinal Peptide (VIP) receptors. In this study, we investigated the presence and characteristics of [125I]PHI binding sites on rat liver membranes. Detergents at nonsolubilizing concentrations (1 mM CHAPS or 0.01% Tween-20) were included in the assay buffer to reduce adsorptive loss of PHI to acceptable levels and permit measurement of PHI-binding to receptors. Under these conditions, binding of PHI to liver membranes was time- and temperature-dependent, reversible and saturable. Unlabeled PHI was 9.7-fold more potent than VIP, and 357-fold more potent than secretin in displacing [125I]-PHI binding. Scatchard analysis suggested the presence of two classes of PHI receptors, with Kd 27 pM and 512 pM. The data from [125I]-PHI and [125I]-VIP binding studies suggested that one class of receptors was PHI-preferring, and the other, equally reactive with PHI and VIP. The concentration of immunoreactive PHI, measured by radioimmunoassay, in blood from the hepatic portal vein of anesthetized rats was 2-fold higher than that from the hepatic vein, suggesting uptake of circulating PHI by the liver.
Paul
S
S
Department of Medicine, Oklahoma University Health Sciences Center, Oklahoma City 73190.
Chou
J
J
Kubota
E
E
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D003902:Detergents / Q000494:pharmacology; D005260:Female; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008297:Male; D010451:Peptide PHI / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011964:Receptors, Gastrointestinal Hormone / Q000378:metabolism*; D018000:Receptors, Peptide; D018005:Receptors, Vasoactive Intestinal Peptide; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism*
D003902:Detergents; C042452:PHI peptide receptor; D010451:Peptide PHI; D011956:Receptors, Cell Surface; D011964:Receptors, Gastrointestinal Hormone; D018000:Receptors, Peptide; D018005:Receptors, Vasoactive Intestinal Peptide; D014660:Vasoactive Intestinal Peptide