Date published: 2025-10-14

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OR4A16 Activators

Chemical activators of OR4A16 can influence its function through various intracellular signaling pathways that ultimately lead to the protein's activation. Isoproterenol, Forskolin, IBMX, Epinephrine, Dopamine, Histamine, Adenosine, PGE2, Salmeterol, and Terbutaline all engage in processes that converge on the elevation of cyclic adenosine monophosphate (cAMP) within olfactory sensory neurons. Isoproterenol, a beta-adrenergic agonist, stimulates the adenylyl cyclase pathway, thereby increasing cAMP levels, which in turn activates protein kinase A (PKA). This activation can lead to the phosphorylation of OR4A16, enhancing its sensitivity. Forskolin directly stimulates adenylyl cyclase, bypassing receptor activation to increase cAMP and stimulate PKA, which then may activate OR4A16. IBMX functions by inhibiting the breakdown of cAMP, sustaining its elevated levels and facilitating the continued activation of PKA and subsequent phosphorylation of OR4A16.

Epinephrine, Dopamine, and Histamine exert their effects by binding to their respective G protein-coupled receptors, which indirectly lead to the activation of adenylyl cyclase and an increase in cAMP production. The resultant PKA activation can lead to the phosphorylation of OR4A16. Adenosine, through its action on A2A receptors, and PGE2, through EP2 and EP4 receptors, also promote the formation of cAMP and subsequent PKA activation, suggesting a similar mechanism of OR4A16 activation. Salmeterol and Terbutaline, both beta2-adrenergic receptor agonists, stimulate adenylyl cyclase activity to increase cAMP levels, which in turn activates PKA and may lead to OR4A16 phosphorylation and activation. Vardenafil and Rolipram, although they target the phosphodiesterase enzymes that break down cyclic guanosine monophosphate (cGMP) and cAMP respectively, also contribute to the activation of PKA due to the resulting increase in cyclic nucleotide levels, which can have a broad impact on sensory signal transduction, including the activation of OR4A16.

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