Noradrenaline increases the expression of the proenkephalin gene in cultured astroglial cells by acting on beta 1- and alpha 1-adrenoceptors.
In primary culture, type I astroglial cells from neocortex of newborn rats express the proenkephalin gene. The glial cells are not homogeneous but differ in their morphology; i.e., polygonal and process-bearing cells are found. Transcription of the proenkephalin gene is increased via protein kinase A upon stimulation with cyclic AMP (cAMP) analogues. In the present study, how noradrenaline affected the expression of the proenkephalin gene in both cell types was investigated. Noradrenaline enhanced the levels of proenkephalin mRNA in a concentration-dependent manner. Experiments with subtype-selective antagonists suggested that beta 1-adrenoceptors were involved. In situ hybridization showed that proenkephalin mRNA was induced only in polygonal cells. Nor-adrenaline also increased the levels of cAMP. However, concentrations of noradrenaline that produced a maximal increase in cAMP caused only submaximal elevations of proenkephalin mRNA. This discrepancy was explained by the finding that noradrenaline increased the expression of the proenkephalin gene also via alpha 1-adrenoceptors. It is concluded that beta 1- and alpha 1-adrenoceptors can act in a synergistic manner on the expression of the proenkephalin gene in astroglial cells.
Hildebrand
B
B
Department of Pharmacology, Freiburg University, Germany.
Olenik
C
C
Theodoridu
A
A
Boeckh
C
C
Uhl
A
A
Meyer
D K
DK
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D004745:Enkephalins / Q000235:genetics*; D015870:Gene Expression / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology*; D009994:Osmolar Concentration; D011498:Protein Precursors / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*
D004745:Enkephalins; D011498:Protein Precursors; D012333:RNA, Messenger; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; C029992:proenkephalin; D000242:Cyclic AMP; D009638:Norepinephrine