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Titolo:
P2Y receptor-mediated inhibition of voltage-activated Ca2+ currents in PC12 cells
Autore:
Vartian, N; Boehm, S;
Indirizzi:
Univ Vienna, Inst Pharmacol, A-1090 Vienna, Austria Univ Vienna Vienna Austria A-1090 Inst Pharmacol, A-1090 Vienna, Austria
Titolo Testata:
EUROPEAN JOURNAL OF NEUROSCIENCE
fascicolo: 5, volume: 13, anno: 2001,
pagine: 899 - 908
SICI:
0953-816X(200103)13:5<899:PRIOVC>2.0.ZU;2-N
Fonte:
ISI
Lingua:
ENG
Soggetto:
SYMPATHETIC TRANSMITTER RELEASE; ADRENAL CHROMAFFIN CELLS; NERVE GROWTH-FACTOR; CALCIUM CURRENT; ADENOSINE TRIPHOSPHATES; NUCLEOTIDE RECEPTORS; PLATELET-AGGREGATION; EXTRACELLULAR ATP; ADP RECEPTOR; G-PROTEINS;
Keywords:
ADP; G-protein; neuronal Ca2+ channel and presynaptic inhibition;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
42
Recensione:
Indirizzi per estratti:
Indirizzo: Boehm, S Univ Vienna, Inst Pharmacol, Waehringerstr 13A, A-1090 Vienna, Austria Univ Vienna Waehringerstr 13A Vienna Austria A-1090 nna, Austria
Citazione:
N. Vartian e S. Boehm, "P2Y receptor-mediated inhibition of voltage-activated Ca2+ currents in PC12 cells", EUR J NEURO, 13(5), 2001, pp. 899-908

Abstract

To search for inhibitory nucleotide receptors in the sympathoadrenal cell lineage of the rat, voltage-activated Ca2+ currents were recorded in PC12 cells after differentiation with nerve growth factor. ADP and ATP, but not uridine nucleotides, reduced Ca2+ current amplitudes and slowed activation kinetics. This effect was mediated by GTP binding proteins, as it was abolished by intracellular GDP betaS and after treatment with pertussis toxin. Furthermore, depolarizations preceding the activation of Ca2+ currents abolished the ADP-induced slowing of activation kinetics and attenuated its inhibitory action on current amplitudes. The modulatory effect of ADP was neither altered in the presence of adenosine receptor antagonists, nor mimicked by agonists at these receptors. In addition, the action of ADP was antagonized by reactive blue 2, but not by suramin or PPADS. Nucleotides tested for their inhibitory action on Ca2+ currents displayed the following rank orderof potency: 2-methylthio-ADP greater than or equal to 2-methylthio-ATP > >ADP betaS > ADP = ATP. When P2X receptors were blocked, the P2X agonists ATP and 2-methylthio-ATP still reduced Ca2+ currents. The P2Y1 receptor antagonists adenosine-2'-phosphate-5'-phosphate and adenosine-3'-phosphate-5'-phosphate did not alter the inhibitory action of ADP, whereas the Sp-isomer of adenosine-5'-O-(1-thiotriphosphate) and 2'- and 3'-O-(4-benzoylbenzoyl)-ATP showed significant antagonistic activity. These results demonstrate that PC12 cells express an as yet unidentified P2Y receptor with pharmacological characteristics similar to those of P2Y1. As receptor-dependent modulation of Ca2+ channels is a key event in presynaptic inhibition, this receptormay correspond to previously described presynaptic nucleotide receptors mediating autoinhibition of sympathetic transmitter release.

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Documento generato il 05/04/20 alle ore 03:40:40