Amastatin and bestatin-induced dipsogenicity in the Sprague-Dawley rat

Intracerebroventricular application of the aminopeptidase inhibitor bestatin, but not amastatin, demonstrated a dose-dependent drinking response. Amastatin is a selective, but not totally specific aminopeptidase inhibitor that blocks aminopeptidase A, which cleaves acidic amino acids, while bestatin selectively blocks aminopeptidase B, which cleaves basic amino acids. Thus, amastatin's major action should be to inhibit angiotensin II (AII) to angiotensin III (AIII) conversion and bestatin's to block AIII degradation. Treatment with the angiotensin receptor antagonist, Sar, Thr-AII (sarthran), completely inhibited bestatin-induced drinking at two different doses. These results support a critical role for the brain-angiotensin system in the ongoing regulation of body fluid homeostasis and suggest an important role for angiotensin III in the brain.