Gustducin - Bitter Transduction

Bitter Transduction

When bitter-stimulated T2R/TRB activate gustducin heterotrimers, gustducin acts to mediate two responses in taste receptor cells. A decrease in cNMPs is triggered by α-gustducin and a rise in IP₃(Inositol trisphosphate)/DAG results from βγ-gustducin. Although the following steps of the α-gustducin pathway are unconfirmed, it is suspected that decreased cNMPs may act on protein kinases which would regulate taste receptor cell ion channel activity. It is also possible that cNMP levels directly regulate the activity of cNMP-gated channels and cNMP-inhibited ion channels expressed in taste receptor cell. The βγ-gustducin pathway continues with the activation of IP₃ receptors and the release of Ca2+ followed by neurotransmitter release.

Bitter taste transduction models Several models have been suggested for the mechanisms regarding the transduction of bitter taste signals.

• Channel blockage: Patch clamping experiments have shown that several bitter ions act directly on potassium channels, blocking them. This suggests that the potassium channels would be located in the apical region of the taste cells. While this theory seems valid, it has only been identified in mudpuppy taste cells.
• Cell-surface receptors: Patch clamping experiments have shown evidence that bitter compounds such as denatonium and sucrose octaacetate act directly on specific cell-surface receptors.
• Direct activation of G proteins: Certain bitter stimulants such as quinine have been show to activate G proteins directly. While these mechanisms have been identified, the physiologic relevance of the mechanism has not yet been established.
• PDE activation: Other bitter compounds, such as thioacetamide and propylthiouracil, have been shown to have stimulatory effects on PDEs. This mechanism has been recognized in bovine tongue epithelium contains fungiform papillae.
• PDE inhibition: Other bitter compounds have been shown to inhibit PDE. Bacitracin and hydrochloride have been show to inhibit PDE in bovine taste tissue

It is thought that these five diverse mechanisms have developed as defense mechanisms. This would imply that many different poisonous or harmful bitter agents exist and these five mechanisms exist to prevent humans from eating or drinking them. It is also possible that some mechanisms can act as backups should a primary mechanism fail. One example of this could be quinine, which has been shown to both inhibit and activate PDE in bovine taste tissue.