Nucleotide-induced Ca2+ signaling in sustentacular supporting cells of the olfactory epithelium.
Extracellular purines and pyrimidines are important signaling molecules acting via purinergic cell-surface receptors in neurons, glia, and glia-like cells such as sustentacular supporting cells (SCs) of the olfactory epithelium (OE). Here, we thoroughly characterize ATP-induced responses in SCs of the OE using functional Ca2+ imaging. The initial ATP-induced increase of the intracellular Ca2+ concentration [Ca2+]i always occurred in the apical part of SCs and subsequently propagated toward the basal lamina, indicating the occurrence of purinergic receptors in the apical part of SCs. The mean propagation velocity of the Ca2+ signal within SCs was 17.10 +/- 1.02 microm/s. ATP evoked increases in [Ca2+]i in both the presence and absence of extracellular Ca2+. Depletion of the intracellular Ca2+ stores abolished the responses. This shows that the ATP-induced [Ca2+]i increases were in large part, if not entirely, due to the activation of G protein-coupled receptors followed by Ca2+ mobilization from intracellular stores, suggesting an involvement of P2Y receptors. The order of potency of the applied purinergic agonists was UTP > ATP > ATPgammaS (with all others being only weakly active or inactive). The ATP-induced [Ca2+]i increases could be reduced by the purinergic antagonists PPADS and RB2, but not by suramin. Our findings suggest that extracellular nucleotides in the OE activate SCs via P2Y2/P2Y4-like receptors and initiate a characteristic intraepithelial Ca2+ wave.
Department of Neurophysiology and Cellular Biophysics, University of Göttingen, Humboldtallee 23, Göttingen, Germany.
Thomas
T
Hassenklöver
Silvia
S
Kurtanska
Ilonka
I
Bartoszek
Stephan
S
Junek
Detlev
D
Schild
Ivan
I
Manzini
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D016764:Cell Polarity / Q000502:physiology; D045604:Extracellular Fluid / Q000378:metabolism; D007424:Intracellular Fluid / Q000378:metabolism; D007814:Larva / Q000033:anatomy & histology / Q000378:metabolism; D009457:Neuroglia / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009711:Nucleotides / Q000378:metabolism* / Q000494:pharmacology; D009831:Olfactory Mucosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D058913:Purinergic Agonists; D058914:Purinergic Antagonists; D058910:Purinergic P2 Receptor Agonists; D058919:Purinergic P2 Receptor Antagonists; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D043562:Receptors, G-Protein-Coupled / Q000187:drug effects / Q000378:metabolism; D011983:Receptors, Purinergic / Q000378:metabolism; D018048:Receptors, Purinergic P2 / Q000378:metabolism; D058473:Receptors, Purinergic P2Y2; D014544:Uridine Triphosphate / Q000378:metabolism / Q000494:pharmacology; D014982:Xenopus laevis / Q000033:anatomy & histology / Q000378:metabolism*
D009711:Nucleotides; D058913:Purinergic Agonists; D058914:Purinergic Antagonists; D058910:Purinergic P2 Receptor Agonists; D058919:Purinergic P2 Receptor Antagonists; D043562:Receptors, G-Protein-Coupled; D011983:Receptors, Purinergic; D018048:Receptors, Purinergic P2; D058473:Receptors, Purinergic P2Y2; C077792:pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid; D011732:Pyridoxal Phosphate; D000255:Adenosine Triphosphate; D002118:Calcium; D014544:Uridine Triphosphate