The Taste of Caffeine

Abstract

Many people avidly consume foods and drinks containing caffeine, despite its bitter taste. Here, we review what is known about caffeine as a bitter taste stimulus. Topics include caffeine's action on the canonical bitter taste receptor pathway and caffeine's action on noncanonical receptor-dependent and -independent pathways in taste cells. Two conclusions are that (1) caffeine is a poor prototypical bitter taste stimulus because it acts on bitter taste receptor-independent pathways, and (2) caffeinated products most likely stimulate "taste" receptors in nongustatory cells. This review is relevant for taste researchers, manufacturers of caffeinated products, and caffeine consumers.

Keywords: TAS2R43; bitterness; caffeine; taste; taste receptors.

FIG. 1.

The canonical taste transduction pathway. Caffeine, and other chemicals that elicit bitter taste sensations, activate T2R-type GPCRs. GPCRs have seven domains that span the plasma membrane. When bitter tasting chemicals bind to T2Rs, this elicits an intracellular signaling cascade that starts with activation of G-proteins (e.g., α-gustducin). Activation of G_α causes the dissociation of βγ subunits, which then activate the enzyme PLCβ2. PLCβ2 then cleaves PIP2 into IP₃. The IP₃ triggers release of calcium from the endoplasmic reticulum by binding to ITPR3s. This calcium release activates and opens TRPM5 leading to sodium influx and depolarization of the taste cell. This depolarization activates voltage-gated sodium channels (VGNC) boosting the depolarization triggered by TRPM5, which triggers the release of ATP through CALHM1 channels. The signal, transmitted by ATP release, is then conveyed to the brain through peripheral nerve fibers that express purinergic receptors. ATP, adenosine triphosphate; T2R, taste 2 receptor; TRPM5, transient receptor potential cation channel subfamily M member 5.

FIG. 2.

Tissue-specific expression of caffeine-responsive T2Rs. The gene IDs for TAS2R7, TAS2R10, TAS2R14, TAS2R43, and TAS2R46 were entered in GENEVESTIGATOR^® and the Agilent Human Gene Expression 8x60K Microarray dataset was selected. In this dataset, TAS2R14 showed the highest expression in most tissues, including the oral cavity. However, TAS2R43 expression was high relative to TAS2R7, 10, 14, and 46 in the pancreas and thymus. Whether or not caffeine modulates the function of tissues in the alimentary, circulatory, integumentary, endocrine, immune, musculoskeletal, nervous, reproductive, respiratory, and urinary systems by acting on caffeine-responsive T2Rs is a relatively unexplored area of research.

FIG. 3.

T2R-independent mechanisms of caffeine taste. Caffeine can inhibit the A2B GPCR and the GABA_A channel on TRCs (A). Caffeine can activate Trpa1 and TRPV1 channels, which are expressed by trigeminal nerve fibers (B). GPCRs, G-protein-coupled receptors; TRCs, taste receptor cells.

FIG. 4.

Intracellular mechanisms of caffeine taste. Caffeine can directly block PDEs, GRKS, and ITPR3 by entering TRCs and other cells. Caffeine can activate RYRs. GRKs, GPCR kinases; PDE, phosphodiesterase; RYRs, ryanodine receptors.