OR5AS1 Activators

OR5AS1 act through various mechanisms to increase intracellular cyclic AMP (cAMP), which can enhance the activity of this olfactory receptor. Isoproterenol, a beta-adrenergic agonist, stimulates beta-adrenergic receptors, leading to the activation of adenylyl cyclase and an increase in cAMP. Similarly, epinephrine and norepinephrine, both of which bind to beta-adrenergic receptors, can raise cAMP levels and thus, can activate OR5AS1. Forskolin serves as a direct stimulator of adenylyl cyclase, thereby boosting cAMP levels and activating OR5AS1. Dopamine can also elevate cAMP by interacting with dopamine receptors that activate Gs proteins, which in turn stimulate adenylyl cyclase. Histamine binds to H2 receptors, and adenosine interacts with A2A and A2B receptors, with both pathways leading to increased cAMP levels and activation of OR5AS1.

Prostaglandin E2 (PGE2) interacts with EP2 and EP4 receptors coupled to Gs proteins, which can amplify cAMP concentrations and activate OR5AS1. IBMX, a non-specific inhibitor of phosphodiesterases, prevents the degradation of cAMP, sustaining its activity and thus, can activate OR5AS1. Vardenafil and sildenafil, primarily known as PDE5 inhibitors, can also increase cAMP levels due to their cross-reactivity with PDEs that degrade cAMP. This rise in cAMP can lead to the activation of OR5AS1. Lastly, rolipram selectively inhibits PDE4, which is responsible for cAMP breakdown. By inhibiting PDE4, rolipram can result in elevated cAMP levels that can activate OR5AS1, completing the array of mechanisms through which these chemical activators enhance OR5AS1 activity.