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Am J Physiol Cell Physiol 285: C1255-C1262, 2003. First published July 2, 2003; doi:10.1152/ajpcell.00149.2003
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RECEPTORS AND SIGNAL TRANSDUCTION

Some sweet and bitter tastants stimulate inhibitory pathway of adenylyl cyclase via melatonin and {alpha}2-adrenergic receptors in Xenopus laevis melanophores

Meirav Zubare-Samuelov,1 Irena Peri,1 Michael Tal,2 Mark Tarshish,3 Andrew I. Spielman,4 and Michael Naim1

1Institute of Biochemistry, Food Science and Nutrition, Faculty of Agricultural, Food and Environmental Quality Sciences, The Hebrew University of Jerusalem, Rehovot 76-100; 2Integrated Genetic Devices, Yavne 81104; and 3Hadassah School of Medicine, Hebrew University of Jerusalem, Jerusalem 91120, Israel; and 4Department of Basic Science and Craniofacial Biology, New York University College of Dentistry, New York, New York 10010

Submitted 15 April 2003 ; accepted in final form 27 June 2003

The sweeteners saccharin, D-tryptophan, and neohesperidin dihydrochalcone (NHD) and the bitter tastant cyclo(Leu-Trp) stimulated concentration-dependent pigment aggregation in a Xenopus laevis melanophore cell line similar to melatonin. Like melatonin, these tastants inhibited (by 45-92%) cAMP formation in melanophores; pertussis toxin pretreatment almost completely abolished the tastant-induced cAMP inhibition, suggesting the involvement of the inhibitory pathway (Gi) of adenylyl cyclase. The presence of luzindole (melatonin receptor antagonist) almost completely abolished the inhibition of cAMP formation induced by saccharin, D-tryptophan, and cyclo(Leu-Trp) but only slightly affected the inhibitory effect of NHD. In contrast, the presence of an {alpha}2-adrenergic receptor antagonist, yohimbine, almost completely abolished the inhibition of cAMP formation induced by NHD but had only a minor effect on that induced by the other tastants. Thus saccharin, D-tryptophan, and cyclo(Leu-Trp) are melatonin receptor agonists whereas NHD is an {alpha}2-adrenergic receptor agonist, but both pathways lead to the same transduction output and cellular response. Formation of D-myo-inositol 1,4,5-trisphosphate (IP3) in melanophores was reduced (15-58%, no concentration dependence) by saccharin, D-tryptophan, and cyclo(Leu-Trp) stimulation but increased by NHD stimulation. Tastant stimulation did not affect cGMP. Although some of the above tastants were found to be membrane permeant, their direct activation of downstream transduction components in this experimental system is questionable. MT1 and MT2 melatonin receptor mRNAs were identified in rat circumvallate papilla taste buds and nonsensory epithelium, suggesting the occurrence of MT1 and MT2 receptors in these tissues. Melatonin stimulation reduced the cellular content of cAMP in taste cells, which may or may not be related to taste sensation.

pigment aggregation; adenosine 3',5'-cyclic monophosphate; D-myo-inositol 1,4,5-trisphosphate; permeation


Address for reprint requests and other correspondence: M. Naim, Institute of Biochemistry, Food Science and Nutrition, Faculty of Agricultural, Food and Environmental Quality Sciences, The Hebrew Univ. of Jerusalem, PO Box 12, Rehovot 76-100, Israel (E-mail: naim{at}agri.huji.ac.il).




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