Aminopeptidase A activity and angiotensin III effects on [Ca2+]i along the rat nephron.
BACKGROUND
This study examined the specific effects of angiotensin III (Ang III) along the nephron.


METHODS
We examined the distribution of aminopeptidase A (APA) activity by using a specific APA inhibitor and by immunostaining with an antirat kidney APA antibody, the Ang III-induced variations of [Ca2+]i by using fura-2 and the characterization of the receptor subtype involved in the response to Ang III in cortical thick ascending limb (CTAL).


RESULTS
APA activity was found all along the nephron but was higher in the cortex than in the medulla. This was confirmed by immunostaining. Increases in [Ca2+]i elicited by 10(-7) mol/liter Ang III were observed all along the nephron. The characterization of the receptor subtype involved in the [Ca2+]i response to Ang III in CTAL indicated that EC50 values for Ang III and Ang II were similar (13.5 and 10.3 nmol/liter, respectively), and Ang III-induced responses were totally abolished by AT1 receptor but not by AT2 receptor antagonists. There was a cross-desensitization of [Ca2+]i responses to 10(-7) mol/liter Ang III and Ang II, and the [Ca2+]i responses to 10(-7) mol/liter Ang II and Ang III were not additive.


CONCLUSIONS
These results show that in CTAL, the [Ca2+]i responses to Ang II and Ang III occur through the same AT1a receptor because this subtype is predominant in this segment. Taken together, these data suggest that APA could be a key enzyme to generate Ang III from Ang II in the kidney.
Hus-Citharel
A
A
INSERM U 36, Paris, France.
Gasc
J M
JM
Zini
S
S
Marchetti
J
J
Roques
B
B
Corvol
P
P
Llorens-Cortes
C
C
D000626:Aminopeptidases / Q000378:metabolism*; D000804:Angiotensin II / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D000805:Angiotensin III / Q000096:biosynthesis / Q000494:pharmacology*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D043384:Glutamyl Aminopeptidase; D007093:Imidazoles / Q000494:pharmacology; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007424:Intracellular Fluid / Q000378:metabolism; D019808:Losartan / Q000494:pharmacology; D008297:Male; D009399:Nephrons / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin / Q000187:drug effects / Q000378:metabolism
D057911:Angiotensin Receptor Antagonists; D007093:Imidazoles; D011725:Pyridines; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin; D000804:Angiotensin II; D000805:Angiotensin III; C073402:PD 123319; C012877:angiotensin II, des-Asp(1)-des-Arg(2)-Ile(5)-; D000626:Aminopeptidases; D043384:Glutamyl Aminopeptidase; D019808:Losartan; D002118:Calcium