Des-Leu angiotensin I: biosynthesis and drinking response

Area of Science:

• Neuroscience
• Biochemistry
• Endocrinology

Background:

• The brain contains enzymes capable of processing angiotensin peptides.
• Angiotensin I (AI) is a precursor peptide in the renin-angiotensin system, involved in blood pressure regulation and fluid balance.

Purpose of the Study:

• To identify and characterize enzymes in brain synaptosomal lysates that metabolize AI.
• To investigate the physiological role of the AI metabolite, des-Leu angiotensin I (AI-dL), in the central nervous system.

Main Methods:

• Preparation of crude synaptosomal lysates from rat and bovine brains.
• Enzymatic assays to determine AI hydrolysis products.
• Biosynthesis and purification of AI-dL.
• Intracerebroventricular injection of AI-dL into rats to assess drinking behavior.
• Pharmacological inhibition of the drinking response using captopril and saralasin.

Main Results:

• Crude rat and bovine synaptosomal lysates hydrolyzed AI to AI-dL but not further.
• A cytosolic enzyme, named angiotensin-related carboxypeptidase (ARC), was identified with specificity for AI.
• Purified AI-dL induced a potent drinking response (dipsogenesis) when injected into rat cerebroventricles.
• The AI-dL-induced drinking response was inhibited by captopril and saralasin, suggesting conversion to angiotensin II (AII).

Conclusions:

• ARC is a novel enzyme in the brain that produces AI-dL from AI.
• AI-dL acts as a dipsogen in rats, likely through its conversion to AII in the brain.
• These findings implicate ARC and AI-dL in the central regulation of water intake and potentially blood pressure.