Noradrenaline transport and transporter mRNA of rat chromaffin cells are controlled by dexamethasone and nerve growth factor.
1. The biochemical basis for differences in noradrenaline (NA) transporter function between chromaffin cells in the adrenal medulla and those maintained in primary culture was investigated. 2. Intact adrenal medullae of neonatal rats accumulated small amounts of [3H]NA. In contrast, dissociated chromaffin cells placed in culture for 2-6 days accumulated 100-1000 times more [3H]NA. 3. Nerve growth factor (NGF) stimulated, whereas glucocorticoids dose dependently and reversibly inhibited, [3H]NA transport in chromaffin cells maintained in culture up to 6 days. During this period, no change in the morphological or biochemical characteristics of either NGF-treated or -untreated chromaffin cells was evident. 4. A rat NA transporter cDNA clone was isolated for use in the quantification of NA transporter mRNA. Intact adrenal medullae contained 40% less NA transporter mRNA than an equivalent number of chromaffin cells in culture. Furthermore, dexamethasone produced nearly 90% loss and NGF elicited approximately 60% increase in NA transporter mRNA levels in cultured cells. 5. In cultured cells, and possibly in vivo, glucocorticoids inhibit NA transporter function of chromaffin cells at least in part through a decrease in NA transporter mRNA.
Wakade
A R
AR
Department of Pharmacology, Wayne State University School of Medicine, Detroit, MI 48201, USA. awakade@cms.cc.wayne.edu
Wakade
T D
TD
Poosch
M
M
Bannon
M J
MJ
D000818:Animals; D001692:Biological Transport; D002478:Cells, Cultured / Q000187:drug effects; D019439:Chromaffin Cells / Q000187:drug effects* / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats
D009414:Nerve Growth Factors; D003907:Dexamethasone; D009638:Norepinephrine