T1R2 and T1R3 subunits are individually unnecessary for normal affective licking responses to polycose: implications for saccharide taste receptors in mice

Treesukosol, Yada; Blonde, Ginger D.; Spector, Alan C.

doi:10.1152/ajpregu.90869.2008

Cited by 85 publications

(122 citation statements)

References 54 publications

(61 reference statements)

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“…In brief two-choice tests, rats preferred a maltooligosaccharide solution containing polymers of 4 to 8 glucose units to solutions containing shorter (maltose, maltotriose) or longer (maltopolysaccharides) glucose polymers (31). The present findings along with those of Treesukosol et al (35) indicate that the presence of either T1R3 or T1R2 is not critical for the taste response to Polycose. Conceivably, either protein alone may function as a glucose polymer receptor.…”

Section: Discussionsupporting

confidence: 67%

“…Nevertheless, the two studies agree in showing that the behavioral response to Polycose, unlike that to sucrose, is largely if not completely spared in T1R3 KO mice. The Treesukosol et al (35) study further revealed that T1R2 KO mice are also normal in their licking response to Polycose solutions. Thus, deletion of either the T1R2 or T1R3 component of the sweet taste receptor largely or completely spares the taste response to glucose polymers.…”

Section: Discussionmentioning

confidence: 92%

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T1R3 taste receptor is critical for sucrose but not Polycose taste

Zukerman

Glendinning²,

Margolskee³

et al. 2009

American Journal of Physiology-Regulatory, Integrative and Comp

115

165

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Zukerman S, Glendinning JI, Margolskee RF, Sclafani A. T1R3 taste receptor is critical for sucrose but not Polycose taste. In addition to their well-known preference for sugars, mice and rats avidly consume starch-derived glucose polymers (e.g., Polycose). T1R3 is a component of the mammalian sweet taste receptor that mediates the preference for sugars and artificial sweeteners in mammals. We examined the role of the T1R3 receptor in the ingestive response of mice to Polycose and sucrose. In 60-s two-bottle tests, knockout (KO) mice preferred Polycose solutions (4 -32%) to water, although their overall preference was lower than WT mice (82% vs. 94%). KO mice also preferred Polycose (0.5-32%) in 24-h two-bottle tests, although less so than WT mice at dilute concentrations (0.5-4%). In contrast, KO mice failed to prefer sucrose to water in 60-s tests. In 24-h tests, KO mice were indifferent to 0.5-8% sucrose, but preferred 16 -32% sucrose; this latter result may reflect the post-oral effects of sucrose. Overall sucrose preference and intake were substantially less in KO mice than WT mice. However, when retested with 0.5-32% sucrose solutions, the KO mice preferred all sucrose concentrations, although they drank less sugar than WT mice. The experience-induced sucrose preference is attributed to a post-oral conditioned preference for the T1R3-independent orosensory features of the sugar solutions (odor, texture, T1R2-mediated taste). Chorda tympani nerve recordings revealed virtually no response to sucrose in KO mice, but a near-normal response to Polycose. These results indicate that the T1R3 receptor plays a critical role in the tastemediated response to sucrose but not Polycose.preference; C57BL/6J mice; chorda tympani nerve; saccharin; postoral conditioning THE TASTE OF SUGAR IS HIGHLY attractive to humans and many other animal species. Studies of inbred mouse strains led to the identification of the T1R2 and T1R3 receptor proteins that dimerize to form a sweet taste receptor (1). Selective elimination of these receptor proteins in knockout mice attenuates or completely blocks the behavioral and gustatory nerve responses to sugars and artificial sweeteners (7, 40). Further, allelic variation in the Tas1r3 gene, which codes for the T1R3 protein (3,(17)(18)(19)24), contributes to strain differences in sensitivity (9), lick responsiveness (8, 10), peripheral taste nerve responsiveness (11), and daily intake and preference (11, 22) for sugars and artificial sweeteners.Sugars are not the only carbohydrates that have an attractive taste to some nonhuman species. Twenty years ago, our laboratory published a series of papers demonstrating that rats, mice, hamsters, and gerbils are strongly attracted to the taste of starch-derived glucose polymers such as Polycose and other maltodextrins (26). Behavioral and electrophysiological evidence indicates that Polycose and sucrose have qualitatively distinct taste sensations in rodents. For example, aversions conditioned to Polycose or sucrose do not cross-generalize, and some ta...

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Section: Discussionsupporting

confidence: 67%

Section: Discussionmentioning

confidence: 92%

T1R3 taste receptor is critical for sucrose but not Polycose taste

Zukerman

Glendinning²,

Margolskee³

et al. 2009

American Journal of Physiology-Regulatory, Integrative and Comp

115

165

View full text Add to dashboard Cite

show abstract

“…In brief-access taste tests, T1R2 KO and T1R3 KO mice are completely unresponsive to artificial sweeteners in contrast to the concentration-dependent responses of WT mice (63,65,71). Like the electrophysiological findings, both T1R2 and T1R3 KO mice show severely blunted unconditioned licking to sucrose, glucose and maltose but display some residual responsiveness at the higher concentrations (71).…”

mentioning

confidence: 74%

Orosensory detection of sucrose, maltose, and glucose is severely impaired in mice lacking T1R2 or T1R3, but Polycose sensitivity remains relatively normal

Treesukosol

Spector

2012

American Journal of Physiology-Regulatory, Integrative and Comp

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Evidence in the literature supports the hypothesis that the T1R2+3 heterodimer binds to compounds that humans describe as sweet. Here, we assessed the necessity of the T1R2 and T1R3 subunits in the maintenance of normal taste sensitivity to carbohydrate stimuli. We trained and tested water-restricted T1R2 knockout (KO), T1R3 KO and their wild-type (WT) same-sex littermate controls in a two-response operant procedure to sample a fluid and differentially respond on the basis of whether the stimulus was water or a tastant. Correct responses were reinforced with water and incorrect responses were punished with a time-out. Testing was conducted with a modified descending method of limits procedure across daily 25-min sessions. Both KO groups displayed severely impaired performance and markedly decreased sensitivity when required to discriminate water from sucrose, glucose, or maltose. In contrast, when Polycose was tested, KO mice had normal EC(50) values for their psychometric functions, with some slight, but significant, impairment in performance. Sensitivity to NaCl did not differ between these mice and their WT controls. Our findings support the view that the T1R2+3 heterodimer is the principal receptor that mediates taste detection of natural sweeteners, but not of all carbohydrate stimuli. The combined presence of T1R2 and T1R3 appears unnecessary for the maintenance of relatively normal sensitivity to Polycose, at least in this task. Some detectability of sugars at high concentrations might be mediated by the putative polysaccharide taste receptor, the remaining T1R subunit forming either a homodimer or heteromer with another protein(s), or nontaste orosensory cues.

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“…The procedural parameters of our brief-access test differed from those used by others (21,46,62) in that animals could initiate as many trials as possible, presented in randomized blocks, during the 30-min session. We chose to do this because 1) it increased the reliability of our estimate of consummatory responding; 2) it provided an assessment of the effect of RYGB on appetitive behavior; and 3) this procedure has been shown to be sensitive to manipulations of the gustatory system (47,(52)(53)(54)(55)65). Tichansky et al (62) also allowed rats to initiate as many trials as possible in 30 min, while Shin et al (46) presented two series of ascending concentrations, and Hajnal et al (21) limited presentations to five or six at each concentration.…”

Section: Effects Of Rygb On Responsiveness To Sucrose In a Briefaccesmentioning

confidence: 99%

Roux-en-Y gastric bypass in rats increases sucrose taste-related motivated behavior independent of pharmacological GLP-1-receptor modulation

Mathes

Bueter

Smith

et al. 2012

American Journal of Physiology-Regulatory, Integrative and Comp

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Roux-en-Y gastric bypass (RYGB) surgery has been shown to decrease consummatory responsiveness of rats to high sucrose concentrations, and genetic deletion of glucagon-like peptide-1 receptors (GLP-1R) has been shown to decrease consummatory responsiveness of mice to low-sucrose concentrations. Here we assessed the effects of RYGB and pharmacological GLP-1R modulation on sucrose licking by chow-fed rats in a brief-access test that assessed consummatory and appetitive behaviors. Rats were tested while fasted presurgically and postsurgically and while nondeprived postsurgically and 5 h after intraperitoneal injections with the GLP-1R antagonist exendin-3(9-39) (30 μg/kg), agonist exendin-4 (1 μg/kg), and vehicle in 30-min sessions during which a sucrose concentration series (0.01-1.0 M) was presented in 10-s trials. Other rats were tested postsurgically or 15 min after peptide or vehicle injection while fasted and while nondeprived. Independent of food-deprivation state, sucrose experience, or GLP-1R modulation, RYGB rats took 1.5-3× as many trials as sham-operated rats, indicating increased appetitive behavior. Under nondeprived conditions, RYGB rats with presurgical sucrose experience licked more to sucrose relative to water compared with sham-operated rats. Exendin-4 and exendin-3(9-39) impacted 0.3 M sucrose intake in a one-bottle test, but never interacted with surgical group to affect brief-access responding. Unlike prior reports in both clearly obese and relatively leaner rats given RYGB and in GLP-1R knockout mice, we found that neither RYGB nor GLP-1R blockade decreased consummatory responsiveness to sucrose in our less obese chow-fed rats. Collectively, these results highlight the fact that changes in taste-driven motivated behavior to sucrose after RYGB and/or GLP-1R modulation are very model and measure dependent.

show abstract

T1R2 and T1R3 subunits are individually unnecessary for normal affective licking responses to polycose: implications for saccharide taste receptors in mice

Cited by 85 publications

References 54 publications

T1R3 taste receptor is critical for sucrose but not Polycose taste

T1R3 taste receptor is critical for sucrose but not Polycose taste

Orosensory detection of sucrose, maltose, and glucose is severely impaired in mice lacking T1R2 or T1R3, but Polycose sensitivity remains relatively normal

Roux-en-Y gastric bypass in rats increases sucrose taste-related motivated behavior independent of pharmacological GLP-1-receptor modulation

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