The a-catulin/dystrophin-associated protein complex regulates GPCR function

1-肾上腺素能受体(ARs)是对交感激素去甲肾上腺素和肾上腺素作出反应的G蛋白偶联受体(GPCRs)，是治疗高血压、良性卧床肥大(BPH)和创伤后应激障碍(PTSD)的治疗靶点。？1-ARs包括3种独特的亚型，？1A、？1B和？1D，它们广泛表达于整个中枢神经系统的血管上。虽然每个亚型都对去甲肾上腺素/肾上腺素作出反应，并激活G？Q/11信号，但？1D-AR亚型使用不同于？1A-AR和？1B-AR亚型的机制发挥特殊的作用。例如，？1D-ARs刺激血管平滑肌细胞迁移，而？1A和？1B-AR亚型刺激血管平滑肌细胞肥大。允许1D-AR选择性激活不同于1A和1B-AR亚型的途径的分子机制仍然是该领域的主要谜团。揭示分子机制？1D-ARs用于刺激血管平滑细胞迁移将发现新的药物靶点，用于治疗中枢神经系统血管再狭窄和动脉粥样硬化斑块形成，预防与恶性高血压相关的偏头痛，降低中风和神经细胞死亡的可能性。

DESCRIPTION (provided by applicant): ?1-adrenergic receptors (ARs) are G-protein coupled receptors (GPCRs) that respond to sympathetic hormones norepinephrine and epinephrine, and are therapeutic targets for the treatment of hypertension, benign prostrate hypertrophy (BPH), and post-traumatic stress disorder (PTSD). ?1-ARs comprise 3 unique subtypes, ?1A, ?1B, and ?1D, which are ubiquitously expressed on blood vessels throughout the CNS. Although each subtype responds to norepinephrine/epinephrine and activates G?q/11 signaling, the ?1D-AR subtype performs a specialized role using mechanisms distinct from the ?1A-AR and ?1B-AR subtypes. For example, ?1D-ARs stimulate vascular smooth muscle cell migration, while the ?1A and ?1B-AR subtypes stimulate vascular smooth cell hypertrophy. The molecular mechanisms that permit ?1D-ARs to selectively activate pathways distinct from those used by the ?1A and ?1B-AR subtypes remains a major mystery in the field. Revealing the molecular mechanisms ?1D- ARs use to stimulate vascular smooth cell migration will identify new drug targets to treat CNS blood vessel restenosis and atherosclerotic plaque formation, prevent migraine associated with malignant hypertension and reduce the potential for stroke and neuronal cell death.