Different calcium-mobilizing receptors share the same guanine nucleotide-binding protein pool in hepatocytes.
High affinity binding of epinephrine to the alpha 1-adrenoceptor reflects the association of the ligand-receptor complex with a guanine nucleotide-binding protein (G protein) and thereby allows the receptor-G protein interaction to be assessed by radioligand binding methods. We have used [3H]prazosin/epinephrine competition binding to rat liver plasma membranes to examine the effects of other Ca(2+)-mobilizing hormones on the interaction between the alpha 1-adrenoceptor and its G protein. The aim of our experiments was to test whether the different Ca(2+)-mobilizing receptors in liver share the same limited pool of G proteins. [Arg8] Vasopressin (AVP) caused a concentration-dependent (EC50 = 0.49 +/- 0.03 nM) inhibition of the extent to which epinephrine formed a high affinity complex with the alpha 1-adrenoceptor; antagonist binding was unaffected by AVP. The effect of AVP was competitively antagonized (Kd = 0.27 +/- 0.10 nM) by a selective peptide antagonist of the V1 vasopressin receptor. We conclude that, in rat hepatocytes, alpha 1-adrenoceptors and V1 vasopressin receptors converge to interact with the same pool of G proteins.
Department of Pharmacology, Cambridge, UK.
L L
LL
Dasso
C W
CW
Taylor
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology; D001667:Binding, Competitive; D002118:Calcium / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism / Q000648:ultrastructure; D002478:Cells, Cultured; D004837:Epinephrine / Q000378:metabolism / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000378:metabolism* / Q000502:physiology; D007545:Isoproterenol / Q000494:pharmacology; D007700:Kinetics; D008099:Liver / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D011224:Prazosin / Q000378:metabolism / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D011956:Receptors, Cell Surface / Q000378:metabolism*; D014316:Tritium
D000318:Adrenergic beta-Agonists; D011942:Receptors, Adrenergic, alpha; D011956:Receptors, Cell Surface; D014316:Tritium; D001127:Arginine Vasopressin; D019204:GTP-Binding Proteins; D007545:Isoproterenol; D002118:Calcium; D011224:Prazosin; D004837:Epinephrine