Evidence against a role for protein kinase C in the regulation of the angiotensin II (AT 1A) receptor

Three putative protein kinase C phosphorylation sites in the carboxyl-terminal region of the angiotensin II AT 1A receptor suggest that protein kinase C is involved in the regulation and desensitisation of this receptor. We investigated this possibility by measuring angiotensin II induced Ca 2+ transients in cultures of neonatal rat cardiac fibroblasts which express predominantly the angiotensin AT 1A receptor. Stimulating or inhibiting protein kinase C activity had no effect on angiotensin II stimulated Ca 2+ transients. In addition, in situ and in vitro kinase assays revealed that a peptide, corresponding to the region of the angiotensin AT 1A receptor containing the protein kinase C sites, was a poor substrate for protein kinase C. Thus, a heterologous desensitising role for this kinase on angiotensin AT 1A receptors in these fibroblasts appears unlikely.