Antagonism of human adiponectin receptors and their membrane progesterone receptor paralogs by TNFalpha and a ceramidase inhibitor.
The progestin and AdipoQ receptor (PAQR) family of proteins comprises three distinct structural classes, each with seemingly different agonist specificities. For example, Class I receptors, like the human adiponectin receptors (AdipoR1 and AdipoR2), sense proteins with a particular three-dimensional fold, while Class II receptors are nonclassical membrane receptors for the steroid hormone progesterone. Using a previously developed heterologous expression system to study PAQR receptor activity, we demonstrate that human PAQRs from all three classes are antagonized by both 1(S),2(R)-d-erythro-2-(N-myristoylamino)-1-phenyl-1-propanol, a ceramidase inhibitor, and TNFalpha, a homologue of adiponectin that functions antagonistically to both adiponectin and progesterone in human cells.
Kupchak
Brian R
BR
Department of Chemistry, University of Florida, P.O. Box 117200, Gainesville, Florida 32611, USA.
Garitaonandia
Ibon
I
Villa
Nancy Y
NY
Smith
Jessica L
JL
Lyons
Thomas J
TJ
D055572:Ceramidases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D008954:Models, Biological; D009226:Myristates / Q000494:pharmacology*; D011412:Propanolamines / Q000494:pharmacology*; D054419:Receptors, Adiponectin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011980:Receptors, Progesterone / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
C475418:ADIPOR1 protein, human; C475420:ADIPOR2 protein, human; D004791:Enzyme Inhibitors; D009226:Myristates; D011412:Propanolamines; D054419:Receptors, Adiponectin; D011980:Receptors, Progesterone; D014409:Tumor Necrosis Factor-alpha; C099657:2-(N-myristoylamino)-1-phenyl-1-propanol; D055572:Ceramidases