Titre du document / Document title

Endothelin (ET)-1-induced inhibition of ATP release from PC-12 cells is mediated by the ET_B receptor : Differential response to ET-1 on ATP, neuropeptide Y, and dopamine levels

Auteur(s) / Author(s)

GARDNER A. ; WESTFALL T. C. ; MACARTHUR H. ;

Résumé / Abstract

During sympathetic neurotransmitter release, there is evidence for differential modulation of cotransmitter release by endothelin (ET)-1. Using nerve growth factor (NGF)-differentiated PC12 cells, the effects of ET-1 on K⁺-stimulated release of ATP, dopamine (DA), and neuropeptide Y (NPY) were quantified using high-pressure liquid chromatography or radioimmunoassay. ET-1, in a concentration-dependent manner, inhibited the release of ATP, but not DA and NPY. Preincubation with the ET_A/B antagonist, PD 142893 (N-acetyl-β-phenyl-D-Phe-Leu-Asp-lle-lle-Trp), reversed the inhibitory effect of ET-1 on ATP release, which remained unaffected in the presence of the ET_A-specific antagonist BQ123 [cyclo(D-Asp-Pro-D-Val-Leu-D-Trp)]. The ET_B agonists, sarafotoxin 6c (Cys-Thr-Cys-Asn-Asp-Met-Thr-Asp-Glu-Glu-Cys-Leu-Asn-Phe-Cys-His-Gln-Asp-Val-lle-Trp), BQ 3020 (N-acetyl-[Ala^11,15]-endothelin 1 fragment 6-21Ac-Leu-Met-Asp-Lys-Glu-Ala-Val-Tyr-Phe-Ala-His-Leu-Asp-lle-lle-Trp), and IRL 1620 (N-succinyl-[Glu⁹, Ala^11,15]-endothelin 1 fragment 8-21Suc-Asp-Glu-Glu-Ala-Val-Tyr-Phe-Ala-His-Leu-Asp-lle-lle-Trp), decreased K⁺-stimulated release of ATP in a dose-dependent manner, and this effect was reversed by the ET_B antagonists RES 701-1 [cyclic (Gly1-Asp9) (Gly-Asn-Trp-His-Gly-Thr-Ala-Pro-Asp-Trp-Phe-Phe-Asn-Tyr-Tyr-Trp)] and BQ 788 (N-[N-[N-[(2,6-dimethyl-1-piperidinyl)carbonyl]-4-methyl-L-leucyl]-1-(methoxycarbonyl)-D-tryptophyl]-D-norleucine sodium salt). Preincubation of PC12 cells with pertussis toxin reversed the ET-1-induced inhibition of the K⁺-evoked ATP release. Real-time intracellular calcium level recordings were performed on PC-12 cell suspensions, and ET-1 induced a dose-dependent decrease in the K⁺-evoked calcium levels. Nifedipine, the L-type voltage-dependent Ca²⁺ channel antagonist, caused inhibition of the K⁺-stimulated ATP release, but the N-type Ca²⁺ channel antagonist, co-conotoxin GVIA, did not reverse the effect on ATP release. These data suggest that ET-1 modulates the release of ATP via the ET_B receptor and its associated G_i/o G-protein through attenuation of the influx of extracellular Ca²⁺ through L-type channels.

Revue / Journal Title

The Journal of pharmacology and experimental therapeutics    ISSN  0022-3565   CODEN JPETAB 

Source / Source

2005, vol. 313, n^o3, pp. 1109-1117 [9 page(s) (article)]

Langue / Language

Anglais

Editeur / Publisher

American Society for Pharmacology and Experimental Therapeutics, Bethesda, MD, ETATS-UNIS  (1909) (Revue)

Localisation / Location

INIST-CNRS, Cote INIST : 548, 35400012475670.0190