Olfactory marker protein (OMP) labels the matured stage of olfactory receptor neurons (ORN) and has promoted the investigation on the physiology of olfaction. OMP regulates olfactory sensitivity and axonal projection of ORNs, both of which are under the control of the olfactory signaling mediator cAMP. Recently, it has been reported that OMP contains cAMP-binding sites. OMP directly captures the photo-uncaged cAMP in the cytosol and rapidly terminates the olfactory cyclic nucleotide-gated (CNG) channels activity to sharpen the olfactory responses. Here, we investigate the contribution of OMP to cAMP acutely produced via activation of G alpha s-protein coupled receptors (GPCR). We expressed OMP and non-desensitizing CNGA2 channels in HEK293T cells together with beta 1-adrenergic receptors (ADRB1) or photo-sensitive beta 2-adrenergic receptors (opto-beta 2). Continuous puff of adrenergic agonist isoproterenol to HEK29T cells with ADRB1 induced the lasting CNGA2 currents in the absence of OMP, while OMP rapidly deactivated the CNGA2 channel activity with residual currents. Photo-activation of opto-beta 2 in the absence of OMP induced the CNGA2 currents with a prolonged increase, while OMP swiftly deactivated the CNGA2 channels after the initial surge. Therefore, cytosolic OMP rapidly uncouples CNGA2 channels and cAMP-signaling produced via GPCRs in the submembrane compartment. (C) 2020 The Authors. Published by Elsevier Inc.