Dexamethasone increases adrenalectomy-depressed Na+,K(+)-ATPase mRNA and ouabain binding in spinal cord ventral horn.
The Na+,K(+)-ATPase plays a key role in the regulation of ion fluxes and membrane repolarization in the CNS. We have studied glucocorticoid effects on biosynthesis of the Na+,K(+)-ATPase and on ouabain binding in the ventral horn of the spinal cord using intact rats, adrenalectomized (ADX) rats, and ADX rats receiving dexamethasone (ADX+DEX) during 4 days. Cryostat sections from spinal cords were incubated with a 35S-oligonucleotide coding for the alpha 3-subunit or a 3H-cDNA coding for the beta 1-subunit of the Na+,K(+)-ATPase using in situ hybridization techniques. In ventral horn motoneurons, grain density per cell and grain density per area of soma for both probes were slightly reduced in ADX rats but significantly increased in the ADX+DEX group, using ANOVA and the Bonferroni's test. Statistical analysis of frequency histograms of neuronal densities further indicated a significant shift to the right for intact rats compared with ADX rats for both probes. Concomitantly, [3H]ouabain binding to membrane preparations from ventral horns was reduced in ADX rats and restored to normal by DEX administration. No effect of adrenalectomy or DEX treatment was obtained in the dorsal horn. In conclusion, glucocorticoids positively modulate the mRNA for the alpha 3-subunit and the beta 1-subunit of the Na+,K(+)-ATPase and recover ouabain binding to normal values. The increments of the synthesis and activity of an enzyme affecting membrane repolarization and synaptic neurotransmission are consistent with the alleged stimulatory effect of glucocorticoids on spinal cord function.
González
S
S
Laboratorio de Bioquímica Neuroendócrina, Instituto de Biología y Experimental-CONICET, Buenos Aires, Argentina.
Grillo
C
C
De Nicola
A G
AG
Piroli
G
G
Angulo
J
J
McEwen
B S
BS
De Nicola
A F
AF
D000315:Adrenalectomy; D000704:Analysis of Variance; D000818:Animals; D000870:Anterior Horn Cells / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D001483:Base Sequence; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005938:Glucocorticoids / Q000494:pharmacology; D006651:Histocytochemistry; D017403:In Situ Hybridization; D008297:Male; D008969:Molecular Sequence Data; D010042:Ouabain / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000254:Sodium-Potassium-Exchanging ATPase / Q000032:analysis / Q000235:genetics*; D013997:Time Factors; D014316:Tritium
D005938:Glucocorticoids; D012333:RNA, Messenger; D014316:Tritium; D010042:Ouabain; D003907:Dexamethasone; D000254:Sodium-Potassium-Exchanging ATPase