Degradation of G11 alpha/Gq alpha is accelerated by agonist occupancy of alpha 1A/D, alpha 1B, and alpha 1C adrenergic receptors.
Cells of clones of rat 1 fibroblasts transfected to express the molecularly defined alpha 1A/D, alpha 1B, or alpha 1C adrenoreceptors and prelabeled with myo-[3H]inositol were each shown to generate high levels of inositol phosphates when exposed to the alpha 1 adrenoreceptor agonist phenylephrine. Maintained exposure of each of these cells to phenylephrine resulted in a large down-regulation of the receptors and also a marked down-regulation of cellular levels of both of the phosphoinositidase C-linked G-proteins Gq alpha and G11 alpha. To examine the mechanism of phenylephrine-induced down-regulation of Gq alpha and G11 alpha, pulse-chase 35S-amino acid labeling experiments were performed with each of the alpha 1A/D, alpha 1B, and alpha 1C adrenoreceptor-expressing cell lines. The rate of degradation of G11 alpha/Gq alpha, which was adequately modeled by a monoexponential with half-life between 33 and 40 h in each of the cell lines in the absence of agonist, was accelerated substantially (some 4-fold) in the presence of phenylephrine. By contrast, the rate of degradation of the G-protein Gi2 alpha, which would not be anticipated to be activated by members of the alpha 1 adrenoreceptor family, was unaltered by the presence of phenylephrine. Levels of mRNA encoding Gq alpha and G11 alpha were not substantially altered by exposure of the cells to phenylephrine in any of the cell lines studied.
Wise
A
A
Division of Biochemistry and Molecular Biology, University of Glasgow, Scotland, United Kingdom.
Lee
T W
TW
MacEwan
D J
DJ
Milligan
G
G
D058646:Adrenergic alpha-1 Receptor Agonists; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D007295:Inositol Phosphates / Q000378:metabolism; D008969:Molecular Sequence Data; D010656:Phenylephrine / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology*
D058646:Adrenergic alpha-1 Receptor Agonists; D000316:Adrenergic alpha-Agonists; D007295:Inositol Phosphates; D012333:RNA, Messenger; D018340:Receptors, Adrenergic, alpha-1; D010656:Phenylephrine; D019204:GTP-Binding Proteins