Novel subtype of human angiotensin II type 1 receptor: analysis of signal transduction mechanism in transfected Chinese hamster ovary cells.
We examined the intracellular signal transduction of two subtypes of human angiotensin II type 1 receptor (AT1aR and AT1bR) by means of the stable expression of each receptor cDNA in Chinese hamster ovary cells. Both receptors showed a rapid stimulation of phosphatidylinositol hydrolysis, a transient increase of intracellular Ca2+ concentration and an inhibitory action on the forskolin-induced cyclic AMP formation. Interestingly, at high AII concentrations (> 1 microM), these AT1bR-mediated responses were inhibited, whereas the AT1aR-mediated responses were not. Thus, the two AT1Rs are considered to be coupled to the same signal transduction cascades, but to be regulated differently on the post-translational level (presumably desensitization).
Kuroda
S
S
Pharmaceutical Group, Takeda Chemical Ind., Ltd., Osaka, Japan.
Konishi
H
H
Okishio
M
M
Fujisawa
Y
Y
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D016466:CHO Cells; D002118:Calcium / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology*; D006224:Cricetinae; D000242:Cyclic AMP / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D006801:Humans; D007295:Inositol Phosphates / Q000378:metabolism; D007700:Kinetics; D010716:Phosphatidylinositols / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D011945:Receptors, Angiotensin / Q000096:biosynthesis / Q000187:drug effects / Q000502:physiology*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D018076:DNA, Complementary; D007295:Inositol Phosphates; D010716:Phosphatidylinositols; D011945:Receptors, Angiotensin; D011994:Recombinant Proteins; D010566:Virulence Factors, Bordetella; D000804:Angiotensin II; D005576:Colforsin; D000242:Cyclic AMP; D002118:Calcium