Effects of the selective protein kinase C inhibitor Ro 31-7549 on human angiotensin II receptor desensitisation and intracellular calcium release.
The mechanism underlying type I angiotensin II (Ang II) receptor (AT1 receptor) desensitisation is unknown. Structural features suggest it may be a substrate for protein kinase C (PKC). The effects of a selective PKC inhibitor, Ro 31-7549, on receptor desensitisation were investigated in CHO cells expressing the human AT1 receptor. Desensitisation was demonstrated with respect to the calcium response to Ang II in Fura-2-loaded cells. Ro 31-7549 had no effect on desensitisation. However, pretreatment with Ro 31-7549 caused a dose-dependent reduction in calcium release from intracellular stores. PKC may therefore act at a locus distal from the receptor itself.
Barker
S
S
Department of Chemical Endocrinology, St. Bartholomew's Hospital Medical College, London, UK.
Kapas
S
S
Fluck
R J
RJ
Clark
A J
AJ
D000804:Angiotensin II / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D016466:CHO Cells; D002118:Calcium / Q000378:metabolism*; D006224:Cricetinae; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D017136:Ion Transport / Q000187:drug effects; D008301:Maleimides / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors* / Q000502:physiology; D011945:Receptors, Angiotensin / Q000235:genetics / Q000502:physiology*; D014162:Transfection
D007211:Indoles; D008301:Maleimides; D011945:Receptors, Angiotensin; D000804:Angiotensin II; D011493:Protein Kinase C; D002118:Calcium; C064755:Ro 31-7549