A cyclic-nucleotide-suppressible conductance activated by transducin in taste cells.
Taste can be divided into four primary sensations: salty, sour, sweet and bitter. Salty and sour are directly transduced by apical channels, whereas sweet and bitter utilize cyclic nucleotide second messengers. We have shown that rod transducin is present in mammalian taste receptor cells, where it is activated by a bitter receptor and in turn activates a phosphodiesterase. Here we introduce into frog taste cells peptides derived from transducin's phosphodiesterase-interaction region, which cause an inward whole-cell current in a subset of cells. We find that the peptides' effects are reversibly suppressed by IBMX and forskolin, indicative of a transducin-activated phosphodiesterase. Cyclic nucleotides suppress the whole-cell current, indicating that cyclic nucleotides may regulate taste-cell conductance. IBMX modifies taste-cell responses to two taste stimuli, implicating phosphodiesterase in taste transduction. Submicromolar cyclic nucleotides directly suppress the conductance of inside-out patches derived from the taste-cell plasma membrane, independently of protein phosphorylation. The channels are unusual in that they are suppressed, rather than activated by cyclic nucleotides. We propose that transducin, via phosphodiesterase, decreases cyclic nucleotide levels to activate the cyclic-nucleotide-suppressible conductance, leading to Ca2+ influx and taste-cell depolarization.
Kolesnikov
S S
SS
Roche Institute of Molecular Biology, Roche Research Center, Nutley, New Jersey 07110, USA.
Margolskee
R F
RF
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology; D006801:Humans; D008564:Membrane Potentials; D009712:Nucleotides, Cyclic / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D011892:Rana catesbeiana; D013649:Taste / Q000502:physiology; D013650:Taste Buds / Q000187:drug effects / Q000378:metabolism*; D015293:Transducin / Q000378:metabolism*
D009712:Nucleotides, Cyclic; D010446:Peptide Fragments; D005576:Colforsin; D010727:Phosphoric Diester Hydrolases; D015293:Transducin; D002118:Calcium; D015056:1-Methyl-3-isobutylxanthine