GPR-137 Activators

GPR-137 can engage in diverse mechanisms to initiate the protein's signaling pathways. Forskolin, by directly stimulating adenylyl cyclase, produces an upsurge in cellular cAMP levels, a critical secondary messenger that activates protein kinase A (PKA). Once activated, PKA can phosphorylate various proteins, including GPR-137, thereby modulating its activity. Similarly, isoproterenol, a non-selective beta-adrenergic agonist, also enhances cAMP concentrations via the beta-adrenergic receptors, setting off a cascade that may culminate in the activation of GPR-137. Prostaglandin E2 (PGE2) and histamine operate through their respective G-protein-coupled receptors, with both agents increasing intracellular cAMP, enabling PKA to potentially modify GPR-137 activity through phosphorylation.

Adrenergic agents, dobutamine and epinephrine, through beta-1 and beta-adrenergic receptors respectively, escalate cAMP levels in certain tissues. Terbutaline and salbutamol, as beta-2 adrenergic receptor agonists, selectively prompt cAMP production in smooth muscle cells, which in turn activates PKA. If GPR-137 is present and responsive in these tissues, PKA could then phosphorylate the protein. Beta-Estradiol, which can activate G-protein-coupled receptors, may also lead to a rise in cAMP and subsequent PKA activation, influencing GPR-137 activity. Additionally, dopamine, through its neuronal G-protein-coupled receptors, and glucagon, by targeting its hepatic receptor, both result in increased cAMP, potentially facilitating GPR-137 phosphorylation via PKA. Lastly, adenosine's modulation of cAMP through its own set of receptors provides yet another avenue for the modulation of GPR-137 activity, assuming the protein is co-expressed and responsive to adenosine receptor activation.