The A1 adenosine receptor is, for most people, a molecular target they can become conscious of when they block it, which happens frequently. Rapid consumption of higher doses of caffeine, in products like Italian espresso or Turkish coffee, provokes a rapid, transient increase in heart rate and a noticeable increase in limb tremor. As the most widely consumed psychoactive substance, caffeine has these effects through blockade of the A1 adenosine receptor, which is found on cardiomyocytes and the peripheral nerve terminals of the sympathetic nervous system (as well as many other locations), leading to an increase in cardiac contractility and noradrenaline release, respectively.
In this report, a 3.6 Å structure of the receptor complexed with the endogenous agonist, adenosine, in the presence of the heterotrimeric G12 protein has been resolved by cryo-EM. As expected, there are differences in conformation compared to the previously-reported antagonist-bound receptor, principally in TM1 and TM2. There are also differences compared to the structure reported for the Gs-coupled, agonist-bound beta2-adrenoceptor.
Comments by Steve Alexander (@mqzspa)
(1) Draper-Joyce C.J. et al. (2018). Structure of the adenosine-bound human adenosine A1 receptor–Gi complex. Nature, 558. 559–563. [PMID: 29925945]