5, 6 In contrast, β 2-AR are prevalent in the respiratory system and cerebellum, and control smooth muscle relaxation processes. β 1-adrenoceptors, which regulate the cardiac output, are mainly located in the heart and cerebral cortex. 1, 3 However, their biological effects are noticeably different, largely due to their different localization in the body. All β-AR mainly induce the production of cAMP from ATP through Gs coupling. 4 β-AR are divided in three subtypes, β 1-, β 2- and β 3-AR. 1- 3 Their crucial role in the regulation of cardiac function and the respiratory system, among others, has signaled them as classical pharmacological targets. Overall, this work provides the first proof of precise control of the therapeutic target β 1-AR in native environments using light.īeta-adrenoceptors (β-AR) are class A G protein-coupled receptors (GPCRs) endogenously activated by the catecholamines adrenaline or noradrenaline, which regulate a variety of biological functions. Strikingly, pAzo-2 also enables a dynamic cardiac rhythm management on living zebrafish larvae using light, thus highlighting the therapeutic and research potential of the developed photoswitches. Moreover, using confocal microscopy we demonstrate that the binding of our best hit, pAzo-2, can be reversibly photocontrolled. All reported molecules allow for an efficient real-time optical control of receptor function in vitro. Here, we report a new strategy for the light-control of β 1-AR activation by means of photoswitchable drugs with a high level of β 1-/β 2-AR selectivity. Although both β 1- and β 2-AR subtypes are expressed in cardiomyocytes, drugs selectively targeting β 1-AR have proven this receptor as the main target for the therapeutic effects of beta blockers in the heart. Catecholamine-triggered β-adrenoceptor (β-AR) signaling is essential for the correct functioning of the heart.
0 kommentar(er)
