Decreases in neurokinin-3 tachykinin receptor-immunoreactive and -mRNA levels are associated with salt appetite in the deoxycorticosterone-treated rat.
Tachykinins are a family of neuropeptides that inhibit salt appetite. Although decreased tachykinin-mRNA levels are observed in natriorexic sodium-deplete rats, no decrease is seen in natriorexic sodium-replete rats that are administered the aldosterone-mimetic deoxycorticosterone acetate (DOCA). Since reduced synthesis of tachykinins could not account for increased appetite, we hypothesized that increased salt appetite was due to a downregulation of tachykinin receptors. Thus, we injected rats with DOCA once daily for 11 days and analyzed tachykinin receptor subtype, neurokinin 3 (NK3r)-immunoreactivity by Western blot analysis since intracerebroventricular injection of senktide (NK3r agonist) attenuates salt intake in DOCA-treated animals. We examined NK3r-immunoreactivity in several brain regions thought to be associated with the control of water and electrolyte balance including the bed nucleus of the stria terminalis, central nucleus of the amygdala, diagonal band of Broca, hippocampus, nucleus tractus solitarius, parabrachial nucleus, paraventricular nucleus of the hypothalamus, and supraoptic nucleus. Consistent with our hypothesis, we found decreased NK3r-immunoreactivity in all brain regions analyzed except for increases in the amygdala and no changes in the paraventricular nucleus of the hypothalamus. To examine whether DOCA's effects on NK3r synthesis are direct, we used differentiated N1E-115 neuroblastoma cells that express NK3r and treated them with a range of concentrations of DOCA and found a dose-dependent decrease in NK3r-mRNA abundance via Northern blotting. The present results suggest that the tachykinin receptors are downregulated after subchronic DOCA treatment and this finding is consistent with the hypothesis that suppressed inhibition of salt appetite as mediated through the tachykininergic system.
Lucas
Louis R
LR
Laboratory of Neuroendocrinology, The Rockefeller University, P O Box 165, 1230 York Avenue, New York, NY 10021, USA. lucasl@rockefeller.edu
Reagan
Lawrence P
LP
Akama
Keith T
KT
Ma
Li-Yun
LY
Tamashiro
Kellie L K
KL
Sakai
Randall R
RR
McEwen
Bruce S
BS
D000818:Animals; D001066:Appetite; D001345:Autoradiography; D015152:Blotting, Northern; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D003864:Depression, Chemical; D003900:Desoxycorticosterone / Q000494:pharmacology*; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D008297:Male; D051379:Mice; D009447:Neuroblastoma / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018042:Receptors, Neurokinin-3 / Q000096:biosynthesis / Q000378:metabolism*; D012982:Sodium, Dietary / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D018042:Receptors, Neurokinin-3; D012982:Sodium, Dietary; D003900:Desoxycorticosterone