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Mapping physiological G protein-coupled receptor signaling pathways reveals a role for receptor phosphorylation in airway contraction

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Aminoglycosides sequestered in lysosomes may overwhelm lysosomal capacity, leading to lysosomal membrane permeabilization and cytosolic release of drug and hydrolases ( Additional preclinical approaches under investigation include MET channel blockers that may prevent aminoglycoside entry into hair cells, intratympanic corticosteroid delivery to achieve high local anti-inflammatory concentrations, caspase and c-Jun N-terminal kinase (JNK) pathway inhibitors targeting apoptotic cell death cascades, and gene therapy strategies to enhance hair cell regeneration or resistance ( Treatment duration optimization Minimizing cumulative aminoglycoside exposure is among the most direct strategies for reducing ototoxic risk