Modulation of glucagon receptor expression and response in transfected human embryonic kidney cells

The modulation of glucagon receptor (GR) expression and biological response was investigated in human embryonic kidney cell (HEK-293) clones permanent ly expressing the GR with different densities. The GR mRNA expression level in these clones was upregulated by cellular cAMP accumulation and presente d a good correlation with both the protein expression level and the maximum number of glucagon binding sites. However, the determination of glucagon-i nduced cAMP accumulation in these cell lines revealed that the enhancement of receptor expression did not lead to a proportional increase in cAMP form ation. Under these conditions, the maximum cAMP production induced by NaF a nd forskolin was not significantly different among selected clones, regardl ess of the receptor expression level. High receptor-expressing clones showe d the greatest susceptibility for agonist-induced desensitization compared with clones with lower GR expression levels. The results of the present stu dy suggest that the GR can recruit non-GR-specific desensitization mechanis m(s). Furthermore, the partial inhibition or alteration of the overall CAMP synthesis pathway at the receptor level may be a necessary adaptive step f or a cell in response to a massive increase in membrane receptor expression level.