A putative role for extracellular ATP: facilitation of 67copper uptake and of copper stimulation of the release of luteinizing hormone-releasing hormone from median eminence explants.
We have previously shown that extracellular copper stimulates the release of the luteinizing hormone-releasing hormone (LH-RH) from explants of the median eminence area (MEA), that chelated copper (Cu) but not ionic Cu is the active form of the metal, and that there is a direct correlation between the ligand specificity for 67Cu uptake and Cu action. In this study, we examined the possibility that extracellular ATP can serve as a ligand facilitating Cu action on the LH-RH neuron. Hypothalamic slices or MEA explants of adult male rats were used. It was found that ATP facilitates 67Cu uptake by hypothalamic slices when Cu:ATP molar ratio was 1:2000 but not 1:2. Keeping the [Cu] constant (150 microM) and varying [ATP], ATP facilitation of Cu stimulation of LH-RH release from MEA explants was found to be a saturable function of [ATP]; maximal facilitation occurred with 2.5 mM ATP. When the nucleotide phosphate specificity for facilitation of Cu action was assessed, ADP, ATP, alpha, beta-methylene-ATP (the non-hydrolyzable analogue of ATP) and GTP were equally effective, whereas AMP and adenosine were ineffective. These results indicate that extracellular ATP can facilitate Cu action on the LH-RH neuron and they are consistent with two mechanisms: (1) ATP facilitating Cu uptake and hence, Cu action and (2) ATP facilitating Cu action via an interaction with a purinergic receptor.
Barnea
A
A
Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas 75235.
Cho
G
G
Katz
B M
BM
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D003300:Copper / Q000493:pharmacokinetics* / Q000494:pharmacology; D003301:Copper Radioisotopes; D005110:Extracellular Space / Q000378:metabolism*; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism*; D008297:Male; D008473:Median Eminence / Q000378:metabolism*; D051381:Rats
D003301:Copper Radioisotopes; D007987:Gonadotropin-Releasing Hormone; D003300:Copper; D000255:Adenosine Triphosphate