Study on the functionality and molecular properties of the AT4 receptor.
Whereas the role of angiotensin II (Ang II) has been clarified in numerous tissues and cell types, the physiological relevance of its C-terminal (3-8) degradation fragment, angiotensin IV (Ang IV), is unclear. Previously, we characterized a specific binding site for Ang IV in the bovine adrenal cortex and on bovine aortic endothelial cells (BAEC). In the present study, we tried to assess the functionality and mechanism of action of this receptor for Ang IV (AT4 receptor). Our results revealed that none of the classical second messengers (i.e., cAMP, Ca2+, inositol phosphates, nitric oxide or arachidonic acid derivatives) was modified significantly during acute (less than 1 h) stimulation of cells with Ang IV. Under normal culture conditions, BAEC efficiently internalized 125I-Ang IV. After a 2 h incubation at 37 degrees C, acid-resistant binding corresponded to about 50% of total cell-associated radioactivity. This rapid internalization process suggests that the AT4 receptor is a functional protein. With a photoaffinity labeling approach, we revealed some properties of the AT4 receptor that are consistent with those of a growth factor or cytokine receptor.
Briand
S I
SI
Department of Pharmacology, Faculty of Medecine, Université de Sherbrooke, Québec, Canada.
Bellemare
J M
JM
Bernier
S G
SG
Guillemette
G
G
D000804:Angiotensin II / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002417:Cattle; D002478:Cells, Cultured; D007425:Intracellular Membranes / Q000378:metabolism; D008970:Molecular Weight; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism; D009994:Osmolar Concentration; D019920:Photoaffinity Labels; D011945:Receptors, Angiotensin / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology*; D015290:Second Messenger Systems / Q000502:physiology
C090830:AT4 receptor; D019920:Photoaffinity Labels; D011945:Receptors, Angiotensin; D000804:Angiotensin II; C012877:angiotensin II, des-Asp(1)-des-Arg(2)-Ile(5)-; D002118:Calcium