Desensitization of P2U receptor in neuronal cell line. Different control by the agonists ATP and UTP, as demonstrated by single-cell Ca2+ responses. 1996

U Czubayko, and G Reiser
Institut für Neurobiochemie, Otto-von-Guericke-Universität Magdeburg, Federal Republic of Germany.

The neuronal cell line NG108-15 (180CC15) responds to extracellular stimuli of ATP or UTP with a transient increase in the level of cytosolic Ca2+. Desensitization was investigated by recording single-cell Ca2+ responses induced by consecutive, regularly spaced (100 s intervals), brief pulses of the nucleotides. The two natural ligands of the P2U receptor, ATP and UTP, were applied at a concentration that evoked responses of a comparable size. With two pulses of UTP (10 microM), a substantial decrease (of 43%) was observed in the size of the second response. The magnitude of response was determined by measuring either the maximal amplitude or the total response, represented by the area of the Ca2+ transient. The analogous studies with ATP pulses showed a much smaller decrease (of 12%). Comparable experiments performed to investigate the mutual interaction between ATP and UTP revealed that after stimulation with ATP the response to UTP was slightly (12%) diminished, whereas the response to ATP after UTP was greatly (52%) decreased. The different degree of desensitization by either UTP or ATP of P2U receptors could be due to (1) a difference in the mode of activation of the receptor by the two ligands or (2) recruitment of another effector mechanism besides elevated Ca2+. Our results indicate the existence of a novel mechanism of receptor control, involving different modes of the receptor, that are induced by two different, activating ligands. We also investigated the crosstalk between the bradykinin B2 receptor and the nucleotide receptor. ATP and UTP, even when eliciting responses of comparable size in the neuronal cell line, affect the desensitization of the bradykinin receptor differently. This suggests regulatory binding sites for the nucleotides on either the nucleotide receptor or the peptide receptor.

UI MeSH Term Description Entries
D009474 Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM. Nerve Cells,Cell, Nerve,Cells, Nerve,Nerve Cell,Neuron
D001920 Bradykinin A nonapeptide messenger that is enzymatically produced from KALLIDIN in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from MAST CELLS during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter. Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg,Bradykinin Acetate, (9-D-Arg)-Isomer,Bradykinin Diacetate,Bradykinin Hydrochloride,Bradykinin Triacetate,Bradykinin, (1-D-Arg)-Isomer,Bradykinin, (2-D-Pro)-Isomer,Bradykinin, (2-D-Pro-3-D-Pro-7-D-Pro)-Isomer,Bradykinin, (2-D-Pro-7-D-Pro)-Isomer,Bradykinin, (3-D-Pro)-Isomer,Bradykinin, (3-D-Pro-7-D-Pro)-Isomer,Bradykinin, (5-D-Phe)-Isomer,Bradykinin, (5-D-Phe-8-D-Phe)-Isomer,Bradykinin, (6-D-Ser)-Isomer,Bradykinin, (7-D-Pro)-Isomer,Bradykinin, (8-D-Phe)-Isomer,Bradykinin, (9-D-Arg)-Isomer,Arg Pro Pro Gly Phe Ser Pro Phe Arg
D002118 Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Coagulation Factor IV,Factor IV,Blood Coagulation Factor IV,Calcium-40,Calcium 40,Factor IV, Coagulation
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D000255 Adenosine Triphosphate An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter. ATP,Adenosine Triphosphate, Calcium Salt,Adenosine Triphosphate, Chromium Salt,Adenosine Triphosphate, Magnesium Salt,Adenosine Triphosphate, Manganese Salt,Adenylpyrophosphate,CaATP,CrATP,Manganese Adenosine Triphosphate,MgATP,MnATP,ATP-MgCl2,Adenosine Triphosphate, Chromium Ammonium Salt,Adenosine Triphosphate, Magnesium Chloride,Atriphos,Chromium Adenosine Triphosphate,Cr(H2O)4 ATP,Magnesium Adenosine Triphosphate,Striadyne,ATP MgCl2
D013498 Suramin A polyanionic compound with an unknown mechanism of action. It is used parenterally in the treatment of African trypanosomiasis and it has been used clinically with diethylcarbamazine to kill the adult Onchocerca. (From AMA Drug Evaluations Annual, 1992, p1643) It has also been shown to have potent antineoplastic properties. Germanin,Moranil,Naganin,Naganol,Naphuride,Suramin Sodium,Suramin, Hexasodium Salt,Suramin, Monosodium Salt,Hexasodium Salt Suramin,Monosodium Salt Suramin,Salt Suramin, Hexasodium,Salt Suramin, Monosodium,Sodium, Suramin
D014407 Tumor Cells, Cultured Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely. Cultured Tumor Cells,Neoplastic Cells, Cultured,Cultured Neoplastic Cells,Cell, Cultured Neoplastic,Cell, Cultured Tumor,Cells, Cultured Neoplastic,Cells, Cultured Tumor,Cultured Neoplastic Cell,Cultured Tumor Cell,Neoplastic Cell, Cultured,Tumor Cell, Cultured
D014544 Uridine Triphosphate Uridine 5'-(tetrahydrogen triphosphate). A uracil nucleotide containing three phosphate groups esterified to the sugar moiety. UTP,Magnesium UTP,Magnesium Uridine Triphosphate,Mg-UTP,Mg UTP,Triphosphate, Magnesium Uridine,Triphosphate, Uridine,UTP, Magnesium
D058473 Receptors, Purinergic P2Y2 A subclass of purinergic P2Y receptors that have a preference for ATP and UTP. The activated P2Y2 receptor acts through a G-PROTEIN-coupled PHOSPHATIDYLINOSITOL and intracellular CALCIUM SIGNALING pathway. P2U Receptor,P2Y2 Receptor,P2U Receptors,P2Y2 Purinoceptor,P2Y2 Receptors,Puringergic Receptor P2Y, G-Protein Coupled, 2,Purinoreceptor P2U,P2Y2 Receptors, Purinergic,Purinergic P2Y2 Receptors,Purinoceptor, P2Y2,Receptor, P2U,Receptor, P2Y2,Receptors, P2U,Receptors, P2Y2
D018048 Receptors, Purinergic P2 A class of cell surface receptors for PURINES that prefer ATP or ADP over ADENOSINE. P2 purinergic receptors are widespread in the periphery and in the central and peripheral nervous system. ADP Receptors,ATP Receptors,P2 Purinoceptors,Purinergic P2 Receptors,Receptors, ADP,Receptors, ATP,ADP Receptor,ATP Receptor,P2 Purinoceptor,Receptor, Purinergic P2,P2 Receptor, Purinergic,P2 Receptors, Purinergic,Purinergic P2 Receptor,Purinoceptor, P2,Purinoceptors, P2,Receptor, ADP,Receptor, ATP

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