Taste Perception

Carbonic anhydrase

permits you to taste beer, champagne, and carbonated beverages Located in close proximity to sour receptors Can be blocked by certain medications Produces H+ from CO2 to allow us to detect carbonated beverages

Taste perception

Bitter, salty, sweet, and umami occur in the brain insular cortex (Not sour). Each flavor has a discrete location

taste areas

Bitter- back of the tongue Sour- sides Sweet- front 1/3 of tongue Salty- OUTER part of front tongue (horseshoe shape) THESE ARE THE CONENTRATIONS OF THE RECEPTORS (THEY ARE ALSO FOUND IN OTHER AREAS)

Sweet and Bitter

Characterized by cAMP increases (by activation of g-coupled protein receptor, then activation of AC -> more cAMP) -cAMP inhibits K channels, thus generating an action potnetial Intracellular calcium stores increase These events lead to action potentials and neurotransmitter release cAMP levels are strongly linked to tasting sweet

T2R Receptors

Found in all taste receptor areas except only a few in the fungiform papillae. The receptor genes are expressed in the same taste cells as gustducin (our original bitter/sweet tested G-coupled protein) T2R5- activated by cycloheximide and relays message to gustducin (which then binds GTP)

How intracellular Ca increases with taste

G-protien becomes active and the alpha subunit binds to GTP to become active This activated alpha subunit binds to phospholipase C (PLC) which ultimately leads to Ca release A different G subunit leads to the activation of AC as described above Ca accumulation is a major factor in driving neurotransmitter release for tasting bitter

Taste receptors are expressed in other tissues

In the gut, we have bitter and sweet receptors that activate the release of gastric hormones (do not synapse in the brain, local response) and glucose transporters to regulate sugar absorption -may help in diabetes and obesity (GYY, GLP-1, and CCK are apatite suppressors and important in insulin regulation)(not a large effector if insulin release) Sour receptor in neural tissues as a pH sensor Bitter taste receptors in ciliated airway epitheial cells (helps with air-born toxic compounds) -also causes the breathing to slow (T2R1s activation, gustducin activation and phospholipase C by intratracheal administration of receptor agonists result in slower breathing in mice.

Sweet taste receptor

Many bitter tasting receptors Few sweet tasting receptors (one pair that is a heterodimer made from 2 different gene products) Bitter has more to protect us from toxic compounds Has many domains that can bind to different activators

Gustducin knock-out mice

Mice no longer avoided bitter substances. Diminished responsiveness to sweets No alterations in responsiveness to sour or salty Diminished action potential of taste cells in response to bitter and sweet substances.

Other systemic taste receptors

Nutrient sensing in the gut by T1R2/T1R3 and GPR120 (fatty acid sensor) is followed by increased secretion of appetite suppressing hormones glucagon-like peptide-1 (GLP-1) and Peptide tyrosine tyrosie (PYY). T2Rs limit absorption of nutrients in the gut.

Sour taste receptors

PKD2L1 is a sour taste receptors. This protein senses low pH (high H+ concentrations). This protein is an ion channel, and activation results in serotonin release. This receptor family was first identified in the kidney, and mutations result in polycystic kidney disease. These receptors were later found to be expressed in taste cells leading to their discovery as sour taste receptors. PKD1L3 was once thought to mediate sour taste sensing, but is now known to be a sodium channel.

The first taste G-protein:Gustducin

Particular G-proteins are dedicated to work with specific receptors. Thus, G-proteins are unique. In addition, G-proteins have common regions or domains, such as GDP/GTP binding domains. It is possible to identify new G-proteins based on common features, but that are uniquely expressed in taste cells.

After taste more changes

Potassium channels are closed and an action potential occurs.

The first identification of a taste receptor

Receptors that work with G-proteins have features unique to each individual receptor, and features common to all receptors in this class. Thus, cDNA libraries made from taste cell RNA's were screened for mRNA's containing the common features of the G-protein receptor class. These first receptors (T1R1 and T1R2) were not always co-expressed with gustducin, however, but otherwise were expressed by taste cells in a way that is consistent with being taste cell receptors (Cell 96, 541 - 551 (1999). -High topographic selectivity -Localized at or near the taste pore of taste buds -Mouse and human genes (orthologues) were identified and cloned in this first study of two putative taste receptor genes

Some practical implications

Structure-based design of new substances with predicted taste -Salt substitutes -Sugar substitutes -Other flavor enhancers New therapeutic strategies New understanding of physiology in other tissues that will help in curing chronic diseases

Five Categories of Taste and Examples

Sweet- carbohydrates (sucrose, glucose) and some amino acids (aspartame) Salty- Monovalent cations (sodium, potassium) Bitter- Many different chemicals are bitter; some of these are toxic Sour- Acids and low pH Umami- (savory) Amino acid or peptide taste enhancers such as monosdium glutamate (MSG)

Taste Receptor Structures and Function

T1R2 + T1R3 (dimer) is the only sweet taste receptor. Different sweet tastants bind to different domains of the receptor, each activating the receptor. There are 30 different bitter taste receptor genes all variants in the T2R family. Each receptor homo and heterodimer recognizes different kinds of bitter tastants. Umami T1R1 + T1R3 dimer, recognizes MSG and other amino acids

Salt taste receptor

TRPV1t when knocked out salt taste is gone Structure consistent with ion channel increases intracellular Ca -> activating PKC and PI3 kinase Mice have 2 receptors and one is an aversion receptor (leads them away from it when salt concentration is high enough) know as epithelial Na channel (ENaC) -blocked by amiloride -don't know if humans have it

How taste gets to the bain

Taste cells could have multiple types of taste receptors, and the final taste sensation could be generated by "blending" these signals in the taste cells or buds. In this model, common afferent nerve fibers would carry a variety of signals to the brain. Signals at the level of the taste bud are interpreted so that neurons can send different signals depending on the input from the taste cell/bud Taste cells may "hard wired" to the brain in a way that communicates the specific flavor. This is known as the labeled line model. Swapping receptors on the same taste cells would test this model. Neuron from the brain detects a specific flavor. This is the case. They switched a sweet receptor to a bitter and when activated the brain received a sweet signal. Different places in the brain are sensitive to different flavors

Function of cell types

Type II cells have taste receptors, but no synaptic contacts. Type II cells signal to Type III cells, that then release neurotransmitters serotonin and ATP. Type IV cell releases serotonin and has synaptic contacts. Type I cells control intercellular fluid ionic make-up (Na+ and K+ levels). (controls communication between cells in the taste bud).

Genetic approach to identify taste receptors

Used an inherited "taste blindness" that was linked to chromosome 5. This lead to a new possible G protein receptor on chromosome 5 Computer analysis lead to further possible receptors on other chromosomes (12 in total) The study estimated 100 related genes (linked to G-coupled taste receptors) in the human genome Main possible receptor T2R (found in human and mice) was then studied)

Cell types in the taste bud

basal cell (undifferentiated) Merkel-like basal cell (type IV) dark cell (type I) light cell (type II) (more mature and diff) intermediate cell (type III)

2nd messengers in taste

cAMP- ATP to cAMP through Adenylate cyclase (phosphodieaterase makes it AMP) cAMP increases in tongue epithelium after sweet taste but this receptor can be blocked by 4,6-dichloro-4,6-dideoxy-a-D-galactopyranoside