Olfactory, Taste, and Photo Sensory Receptors in Non-sensory Organs: It Just Makes Sense

Abstract

Sensory receptors that detect and respond to light, taste, and smell primarily belong to the G-protein-coupled receptor (GPCR) superfamily. In addition to their established roles in the nose, tongue, and eyes, these sensory GPCRs have been found in many 'non-sensory' organs where they respond to different physicochemical stimuli, initiating signaling cascades in these extrasensory systems. For example, taste receptors in the airway, and photoreceptors in vascular smooth muscle cells, both cause smooth muscle relaxation when activated. In addition, olfactory receptors are present within the vascular system, where they play roles in angiogenesis as well as in modulating vascular tone. By better understanding the physiological and pathophysiological roles of sensory receptors in non-sensory organs, novel therapeutic agents can be developed targeting these receptors, ultimately leading to treatments for pathological conditions and potential cures for various disease states.

Keywords: G-protein couple receptor; bitter taste receptor; olfactory receptor (OR); opsins; sensory receptor.

Figure 1

Mechanisms proposed to explain how bitter taste receptor (TAS2R) agonists cause airway smooth muscle (ASM) cell relaxation. Deshpande et al. (1) proposed that activation of the TAS2R caused activation of gusticin, followed by Gβγ and phospholipase C (PLC) subunits, to activate inositol triphosphate (IP3), which in turn activates the IP3 receptor to release calcium (Ca²⁺) from the sarcoplasmic reticulum. This release of calcium causes opening of the BK_Ca-channel and efflux of potassium (K⁺) that hyperpolarizes and relaxes the ASM cell. Zhang et al. (2) proposed that TAS2R activation leads to small, incremental increases in Ca²⁺, which causes closure of membrane Ca²⁺ channels. This closure inhibits Ca²⁺ influx, cell depolarization, and cell contraction, leading to cellular relaxation. Tan et al. (3) proposed that TAS2R activation causes a change in Ca²⁺ sensitivity and/or changes to Ca²⁺ oscillation that inhibit Ca²⁺ release from the sarcoplasmic reticulum, thereby inhibiting cellular contraction.

Figure 2

Effects of light exposure on pulmonary artery relaxation. (A) Relaxation of control (WT), Opn4 knockout (Opn4^−/−), and Opn3sh-treated mouse pulmonary arteries exposed to specific light wavelengths in 30 nm increments. (B) Representative traces show pulmonary arterial pressure (P_PA) of isolated perfused rat lungs subject to hypoxia-induced pulmonary hypertension (HPV). Lungs were exposed to blue light with/without GRK2 inhibitor at peak pressure. (C) Statistical comparison of changes in P_PA after HPV with/without blue light and GRK2 inhibitor. *P < 0.05. Reproduced with permission from Barreto Ortiz et al. (2018).