DEGRADATION OF G(11)ALPHA/G(Q)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-[H-3]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 G(q) alpha and G(11)alpha. To examine the mechanism of phenylephrine-induced down-regulation of G(q) alpha and G(11)alpha, pulse-chase S-35-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 G(11)alpha/G(q) 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 G(i)2 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 G(q) alpha and G(11)alpha were not substantially altered by exposure of the cells to phenylephrine in any of the cell lines studied.