Evidence against a role for protein kinase C in the regulation of the angiotensin II (AT1A) receptor.
Three putative protein kinase C phosphorylation sites in the carboxyl-terminal region of the angiotensin II AT1A 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 Ca2+ transients in cultures of neonatal rat cardiac fibroblasts which express predominantly the angiotensin AT1A receptor. Stimulating or inhibiting protein kinase C activity had no effect on angiotensin II stimulated Ca2+ transients. In addition, in situ and in vitro kinase assays revealed that a peptide, corresponding to the region of the angiotensin AT1A 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 AT1A receptors in these fibroblasts appears unlikely.
Thomas
W G
WG
Weis Center for Research, Geisinger Clinic, Danville, PA, USA.
Baker
K M
KM
Booz
G W
GW
Thekkumkara
T J
TJ
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D006321:Heart / Q000187:drug effects; D011493:Protein Kinase C / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011945:Receptors, Angiotensin / Q000187:drug effects* / Q000378:metabolism
D011945:Receptors, Angiotensin; D000804:Angiotensin II; D000255:Adenosine Triphosphate; D011493:Protein Kinase C; D002118:Calcium