Inhibition of cyclic 3′, 5′‐nucleotide phosphodiesterase in bovine taste papillae by bitter taste stimuli

Kurihara, Kenzo

doi:10.1016/0014-5793(72)80640-9

Cited by 54 publications

(15 citation statements)

References 10 publications

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“…Ozeki [51] correctly predicted that quinine decreases the K conductance of TRCs. The membrane-permeant bitter taste stimuli quinine and strychnine, like methylxanthines, were reported to affect the activity of the cAMP-phosphodiesterase of TRCs [31,34,54]. It seemed interesting, therefore, to search for membrane effects elicited by IBMX and cAMP.…”

Section: Ca Currentsmentioning

confidence: 98%

Patch-clamp study of isolated taste receptor cells of the frog

1987

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Taste discs were dissected from the tongue of R. ridibunda and their cells dissociated by a collagenase/low Ca/mechanical agitation protocol. The resulting cell suspension contained globular epithelial cells and, in smaller number, taste receptor cells. These were identified by staining properties and by their preserved apical process, the tip of which often remained attached to an epithelial (associated) cell. When the patch pipette contained 110 mM KCl and the cells were superfused with NaCl Ringer's during whole-cell recording, the mean zero-current potential of 22 taste receptor cells was -65.2 mV and the slope resistance 150 to 750 M omega. Pulse-depolarization from a holding voltage of -80 mV activated a transient TTX-blockable inward Na current. Activation became noticeable at -25 mV and was half-maximal at -8 mV. Steady-state inactivation was half-maximal at -67 mV and complete at -50 mV. Peak Na current averaged -0.5 nA/cell. The Ca-ionophore A23187 shifted the activation and inactivation curve to more negative voltages. Similar shifts occurred when the pipette Ca was raised. External Ni (5 mM) shifted the activation curve towards positive voltages by 10 mV. Pulse depolarization also activated outward K currents. Activation was slower than that of Na current and inactivation slower still. External TEA (7.5 mM) and 4-amino-pyridine (1 mM) did not block, but 5 mM Ba blocked the K currents. K-tail currents were seen on termination of depolarizing voltage pulses. A23187 shifted the IK(V)-curve to more negative voltages. Action potentials were recorded when passing pulses of depolarizing outward current. Of the frog gustatory stimulants, 10 mM Ca caused a reversible 5- to 10-mV depolarization in the current-clamp mode. Quinine (0.1 mM, bitter) produced a reversible depolarization accompanied by a full block of Na current and, with slower time-course, a partial block of K currents. Cyclic AMP (5 mM in the external solution or 0.5 microM in the pipette) caused reversible depolarization (to -40 to -20 mV) due to partial blockage of K currents, but only if ATP was added to the pipette solution. Similar responses were elicited by stimulating the adenylate cyclase with forskolin. Blockage of cAMP-phosphodiesterase enhanced the response to cAMP. These results suggest that cAMP may be one of the cytosolic messengers in taste receptor cells. Replacement of ATP by AMP-PNP in the pipette abolished the depolarizing response to cAMP.(ABSTRACT TRUNCATED AT 400 WORDS)

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Section: Ca Currentsmentioning

confidence: 98%

Patch-clamp study of isolated taste receptor cells of the frog

1987

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“…Elevations of intracellular calcium have been reported for several bitter stimuli, such as denatonium (3,7,39), as well as for certain sweet stimuli (4). Various phosphodiesterases have been reported to be expressed in taste receptor cells (32) and may be substrates for particularly bitter stimuli (28,42) or via activation of the gustducin pathway. Moreover, a role for stimulus-induced activation of adenosine receptors has been proposed in taste sensations (49,50), where activation of adenosine receptor, by caffeine or other methylxanthines, may act to intensify the perception of certain sweeteners.…”

mentioning

confidence: 99%

“…Modulation of second messengers may occur in a receptor-independent manner via direct stimulatory interactions on G proteins that further activate downstream transduction cascades (36,41) or by direct interaction with enzymes that degrade cyclic nucleotides (28,42). Particularly bitter stimuli (caffeine and theophylline) were measured to increase cGMP, whereas others (strychnine and denatonium) were ineffective.…”

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confidence: 99%

Dual actions of caffeine on voltage-dependent currents and intracellular calcium in taste receptor cells

Zhao¹,

Lu²,

Herness

2002

American Journal of Physiology-Regulatory, Integrative and Comp

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-Although the numerous stimuli representing the taste quality of bitterness are known to be transduced through multiple mechanisms, recent studies have suggested an unpredicted complexity of the transduction pathways for individual bitter stimuli. To investigate this notion more thoroughly, a single prototypic bitter stimulus, caffeine, was studied by using patch-clamp and ratiometric imaging techniques on dissociated rat taste receptor cells. At behaviorally relevant concentrations, caffeine produced strong inhibition of outwardly and inwardly rectifying potassium currents. Caffeine additionally inhibited calcium current, produced a weaker inhibition of sodium current, and was without effect on chloride current. Consistent with its effects on voltage-dependent currents, caffeine caused a broadening of the action potential and an increase of the input resistance. Caffeine was an effective stimulus for elevation of intracellular calcium. This elevation was concentration dependent, independent of extracellular calcium or ryanodine, and dependent on intracellular stores as evidenced by thapsigargin treatment. These dual actions on voltageactivated ionic currents and intracellular calcium levels suggest that a single taste stimulus, caffeine, utilizes multiple transduction mechanisms. sensory transduction; bitter; patch clamp; fura 2; ratiometric imaging TASTE RECEPTOR CELLS CONVEY gustatory information from the oral cavity to afferent nerve fibers that, in turn, relay their activation to the central nervous system. Our present understanding of these processes suggests that not only do different transduction mechanisms exist for the varying qualities of taste but multiple mechanisms exist within a taste quality (15,18). Bitter stimuli, in particular, comprise a particularly heterogeneous group of chemically diverse compounds. For example, alkaloids, glucosides, divalent cations, methylated or acetylated carbohydrates, amino acids, and dipeptides are reported to produce bitter sensations in humans. It is not surprising that a number of mechanisms might be required for this wide array of chemically diverse compounds. Moreover, because many bitter compounds are toxic, there exists an evolutionary advantage to evolve multiple mechanisms to sense noxious stimuli. The details of these transduction mechanisms are the subject of this study.Bitter stimuli have been proposed to utilize transduction pathways that include receptor-mediated production or inhibition of second-messenger molecules, modulation of second-messenger molecules by direct interaction with G proteins or degradative enzymes such as phosphodiesterase, or direct block of ion channels. Many bitter stimuli are proposed to be transduced via the gustducin pathway. Gustducin, a G protein expressed in 20-30% of taste receptor cells, shares considerable homology with transducin in photoreceptors (31). By analogy to transducin, the activation of gustducin by a seven-transmembrane receptor is suggested to stimulate phosphodiesterase, thereby lowering cyclic nucleotide...

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“…Based on the striking similarity of ␣-gustducin to ␣-transducin (1, 7), the presence of both of these ␣-subunits in TRCs (2), and the high levels of phosphodiesterase (PDE) in taste tissue (8,9), it was proposed that bitter transduction is mediated by way of ␣-gustducin activation of taste PDE. Consistent with this proposal, PDE from bovine taste tissue is activated in vitro by ␣-gustducin and ␣-transducin (2,10).…”

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confidence: 99%

Dominant loss of responsiveness to sweet and bitter compounds caused by a single mutation in α-gustducin

Ruiz-Avila

Wong

Damak

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

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Biochemical and genetic studies have implicated ␣-gustducin as a key component in the transduction of both bitter or sweet taste. Yet, ␣-gustducin-null mice are not completely unresponsive to bitter or sweet compounds. To gain insights into how gustducin mediates responses to bitter and sweet compounds, and to elicit the nature of the gustducin-independent pathways, we generated a dominant-negative form of ␣-gustducin and expressed it as a transgene from the ␣-gustducin promoter in both wild-type and ␣-gustducin-null mice. A single mutation, G352P, introduced into the C-terminal region of ␣-gustducin critical for receptor interaction rendered the mutant protein unresponsive to activation by taste receptor, but left its other functions intact. In control experiments, expression of wild-type ␣-gustducin as a transgene in ␣-gustducin-null mice fully restored responsiveness to bitter and sweet compounds, formally proving that the targeted deletion of the ␣-gustducin gene caused the taste deficits of the null mice. In contrast, transgenic expression of the G352P mutant did not restore responsiveness of the null mice to either bitter or sweet compounds. Furthermore, in the wild-type background, the mutant transgene inhibited endogenous ␣-gustducin's interactions with taste receptors, i.e., it acted as a dominant-negative. That the mutant transgene further diminished the residual bitter and sweet taste responsiveness of the ␣-gustducin-null mice suggests that other guanine nucleotide-binding regulatory proteins expressed in the ␣-gustducin lineage of taste cells mediate these responses.

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Inhibition of cyclic 3′, 5′‐nucleotide phosphodiesterase in bovine taste papillae by bitter taste stimuli

Cited by 54 publications

References 10 publications

Patch-clamp study of isolated taste receptor cells of the frog

Patch-clamp study of isolated taste receptor cells of the frog

Dual actions of caffeine on voltage-dependent currents and intracellular calcium in taste receptor cells

Dominant loss of responsiveness to sweet and bitter compounds caused by a single mutation in α-gustducin

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