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NAPE-PLD is target of thiazide diuretics
Sara Chiarugi1, Francesco Margheriti1, Valentina De Lorenzi2
1BioStructures Lab, Istituto Italiano di Tecnologia (IIT@NEST), Piazza San Silvestro 12, 56127 Pisa, Italy; Laboratorio NEST, Scuola Normale Superiore, Piazza San Silvestro 12, 56127 Pisa, Italy.
Cell Chemical Biology
|February 25, 2025
Summary
Thiazide diuretics
Area of Science:
- Pharmacology
- Cardiovascular Medicine
- Neuroscience
Background:
- Thiazide diuretics are widely used for hypertension and edema.
- Their long-term mechanism for reducing blood pressure remains unclear.
- Existing research has not identified the specific molecular targets.
Purpose of the Study:
- To identify the molecular target and mechanism of action for thiazide diuretics.
- To elucidate how these drugs achieve chronic blood pressure reduction.
- To explore potential therapeutic applications for related neurological disorders.
Main Methods:
- Discovery and validation of a novel drug target.
- Structural and functional analysis of the target.
- Preclinical studies using hypertensive rat models.
Main Results:
- Identified N-acylphosphatidylethanolamine-specific phospholipase D (NAPE-PLD) as a key target.
- Demonstrated NAPE-PLD's role in both acute diuresis and chronic antihypertensive effects.
- Revealed the molecular basis for thiazide's dual action.
Conclusions:
- NAPE-PLD is a previously unrecognized target for thiazide diuretics.
- This discovery clarifies the mechanism of thiazide-induced hypertension treatment.
- Findings may guide the development of new treatments for vascular and neurological conditions.
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