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. CONCLUSION: 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.[1]References
- Aminopeptidase A activity and angiotensin III effects on [Ca2+]i along the rat nephron. Hus-Citharel, A., Gasc, J.M., Zini, S., Marchetti, J., Roques, B., Corvol, P., Llorens-Cortes, C. Kidney Int. (1999) [Pubmed]
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