Sucrose is a crystalline disaccharide composed of the monosaccharides glucose and fructose. It is commonly known as table sugar and sometimes is called saccharose. It occurs naturally in most plants and is obtained commercially especially from sugarcane or sugar beets . Best known for its nutritional role, it is used extensively as a food and a sweetener. It is the prototypical example of a sweet substance. Sucrose in solution has a sweetness perception rating of 1 and other substances are rated relative to this.
Sweet taste receptors
The ability to perceive sweet taste resides in taste buds on the tongue.
The sweet taste modality is mediated by a small family of three G-protein-coupled receptors: T1R1, T1R2 and T1R3 (GPCRs). These GPCRs assemble into either homodimeric and heterodimeric receptor complexes and are characterized by the presence of long ammino-terminal extracellular domains that are believed to mediate ligand recognition and binding.
The critical role of T1Rs in sweet taste detection and perception emerged from an ensemble of studies, including the characterization of T1R expression profiles, the analysis of naturally occurring sweet receptor mutants (and the identification of species-specific differences in sweet taste preferences), functional experiments in cell based essays and the generation of genetically modified mouse lines. More than 30 years ago, genetic studies of sweet taste in mice identified a single principal locus that influences response to different sweet substances. This locus known as Sac determines threshold differences in the ability of some strains to distinguish sucrose- and saccharin- containing solutions from water. In 2001 Sac was shown by linkage analysis and genetic rescue to encode T1R3. Indeed, functional expression studies in heterologous cells revealed that T1R3 combines with T1R2 (T1R2+3) to form a sweet taste receptor that respond to all classes of sweet tastants.
Mammalian sweet taste receptors, 2001
T1Rs are expressed in subsets of taste-receptors cells, and their expression pattern defines three cell types taste-receptor cells expressing T1R1 and T1R3 (T1R1+3 cells), taste-receptor cells co-expressing T1R2 and T1R3 (T1R2+3 cells) and taste-receptor cells containing T1R3 alone.
Recently, biochemical studies of human, rodent and chimaeric human-rodent T1R2+3 receptors have shown that diverse classes of sweet-receptor ligands actually require different domains of the receptor complex for recognition. Together, these genetic, functional and biochemical studies have validated the role of the T1R2 and T1R3 subunits in sweet-tastant recognition, and demonstrated the importance of heteromerization in receptor function.
The hetrodimeric sweet taste receptor has multiple potential ligand binding sites, 2006
The sweet taste receptor: a single receptor with multiple sites and modes of interaction, 2007
Sweet taste in man: a review, 2008
Sweet receptor pathways
Taste transduction typically utilizes two or more pathways in parallel. Sweet-sensitive taste cells of the rat appear to respond to sucrose with a conformational change in the molecule. This change activates the G-protein, gustducin, which in turn activates adenylate cyclase. Adenylate cyclase catalyzes the conversion of ATP to cAMP, followed by adenosine 3',5'-cyclic monophosphate (cAMP)-dependent membrane events. First of all, the cAMP molecule activates a protein kinase, which in turn phosphorylates and closes a potassium ion channel. Consequently, the excess potassium ions increase the positive charge within the cell causing voltage-gated calcium ion channels to open, further depolarizing the cell. The increase in calcium ultimately causes neurotransmitter release, which is then received by a primary afferent neuron.
The same cells respond differently to some artificial sweeteners, with activation of phospholipase C (PLC) followed by inositol 1,4,5-trisphosphate (IP3)-dependent Ca2+ release from intracellular stores.
Ascending central gustatory pathway
The above-stated neurotrasmitter release activates primary afferent neuron, in this way taste-specific informations are conveyed by cranial nerves VII, IX and X to the rNTS (rostral division of the nucleus tractus solitarius) in the medulla. In primates, fibers from second-order taste neurons in the rNTS project ipsilaterally to the VPMpc (parvicellular part of the ventroposterior medial) nucleus of the thalamus. Thalamic efferents project to the insula, defining the primary gustatory cortex (GC) which, in turn, projects to the orbitofrontal cortex (OFC), sometimes defined as a secondary cortical taste area. Cortical gustatory regions also project to areas of the ventral forebrain, such as the amygdala.
Animal models suggest that sucrose activates taste afferents differently than non-caloric sweeteners. Both sucrose and artificial sweeteners activate functionally connected primary taste pathways. Pleasantness slopes for both sweet stimuli predicted significant left insula activation; however sucrose elicits a stronger brain response in the anterior insula, frontal operculum, striatum and anterior cingulate, compared to artificial sweeteners. Only sucrose, but not non-caloric sweeteners, stimulation engages dopaminergic midbrain areas in relation to the behavioral pleasantness response. This may indicate that sucrose is able to cause a different physiological brain response compared to sucralose with recruitment of more food reward-related brain regions, despite the inability of subjects to consciously distinguish the tastes.
Sucrose activates human taste pathways differently from atrificial sweetener, 2008
Oral sucrose as an analgesic drug for procedural pain in newborn infants
Many infants admitted to hospital undergo repeated invasive procedures such as the taking of a blood sample, subcutaneous injections, vaccinations and heel-sticks. Oral sucrose is frequently given to relieve procedural pain in neonates on the basis of its effect on behavioural and physiological pain scores (the pain perception is estimated essentially considering the cry length and facial expressions). The concentration of sucrose for use in infant pain management typically varies between 12% and 24%, and the volume varies from 0,5 ml for preterm infants to 2 ml for term infants. The sucrose may be administered to infants by dipping a pacifier into the sucrose solution.
Sucrose for analgesia in newborn infants undergoing painful procedures, 2010
How sucrose solutions mediate analgesia
Sucrose was originally believed to activate "mu opioid receptors": http://en.wikipedia.org/wiki/%CE%9C-opioid_receptor but this hypothesis was not confirmed by researches.
Sugar Solution Analgesia: The Effects of Glucose on Expressed Mu Opioid Receptors, 2005
The calming and pain-relieving effects of sucrose are thought to be mediated by "endogenous opioid": http://18.104.22.168/boundary/addiction/endogenous_opiates_physiological_role.pdfpathways activated by sweet taste.
Sucrose analgesia: absorbptive mechanism or taste perception?, 1999
Mechanisms of sucrose and non-nutritive sucking in procedural pain management in infants, 2001
Recently has been conducted many studies aimed to investigate the central pathways by which taste stimuli engage neural antinociceptive mechanisms. Sucrose has been founded to activate neurons of many encephalic sites – such as the rostral nucleus tractus solitarius, periaqueductal gray, the nucleus raphe magnus – in common between the above-stated ascending gustatory pathway and descending pain pathway.
Brainstem substrate for analgesia elicited by intraoral sucrose, 2005
The descending pain modulation is mediated by endogenous opioid which activate opioid receptors (a group of G protein-coupled receptors).
Comparing analgesia and μ-opioid receptor internalization produced by intrathecal encephalin, 2007
Antinociception induced by acute oral administration of sweet substance in young and adult rodents: the role of endogenous opioid peptides chemical mediators and μ(1)-opioid receptors, 2011
Preference for sweet taste
Endogenous opioids within the central nervous system are postulated to mediate hedonic aspects of feeding behavior and in particular they can be involved in preference for sweet taste.
Taste responses and preferences for sweet high-fat foods: evidence for opioid involvement, 1992
Endogenous opioid encode relative taste preference: 2006
The relationship between opioid and sugar intake: review of evidence and clinical applications, 2010
Opioid peptides are heavily expressed throughout the limbic system and linked to dopamine systems in many parts of the forebrain .The endogenous opioid systems exert some of their effects on reinforcement processing by interacting with DA systems. The opioid peptide enkephalin in the Nucleus Accumbens has been related to reward and can activate both mu and delta receptors to increase the release of DA.
Taste pathways flow from brainstem visceral taste nuclei (NTS, nucleus of the solitary tract and parabrachial nucleus) and gustatory cortex. Further routes include projections to amygdala, where motivational value of taste may be encoded. A direct projection from NTS to accumbens shell is also noted, thereby enabling integration of input from association cortex and other limbic structures with brainstem information. Interface between taste perception and evaluation with response selection is proposed to take place in the ventral striatum. Outflow from ventral striatum is through several routes, namely through the hypothalamus and basal ganglia output structures.
Opioid modulation of taste hedonics within the ventral striatum, 2002
"The ventral pallidum and hedonic reward: neurochemical maps of sucrose "liking" and food intake, 2005":http://www.ncbi.nlm.nih.gov/pubmed/16177031
Sucrose and obesity
Several studies have correlated the rise in the incidence of obesity with an increase in sugar consumption.
Sugar intake may lead to an increased number of and/or affinity for opioid receptors.
Sugar, opioids and binge eating, 1985
The involvement of the DA system in reward and reinforcement has led to the hypothesis that alterations in DA activity in obese subjects dispose them to excessive use of food. Exposure to especially palatable foods, activates the several brain regions including the anterior insula and right orbitofrontal cortex , which may underlie the motivation to procure food.
Sugars: hedonic aspects, neuroregulation, and energy balance, 2003
Hedonic hot spots in the brain, 2006