Induction of c-fos and TIS genes in cultured rat astrocytes by neurotransmitters.
The interaction of neurotransmitters with their specific receptors initiates a cascade of intracellular biochemical events which lead to induction of specific genes. Included in this cascade is the rapid and transient induction of a family of primary early response genes we term TIS genes (Lim et al.: Oncogene 1: 263-270, 1987). Expression of six TIS gene, including c-fos, was examined in secondary cultures of rat neocortical astrocytes exposed to muscarinic and adrenergic agonists and antagonists to study the early genomic responses which accompany neurotransmitter-induced alteration of glial morphology and physiology. Carbachol induced accumulation of mRNA for c-fos and the other TIS genes. Carbachol-mediated induction of TIS mRNA expression was sensitive to atropine blockade and was potentiated by lithium. Norepinephrine (NE), isoproterenol, or phenylephrine also induced TIS mRNA accumulation. In order to determine which second-messenger pathways mediate NE induction of TIS gene expression, the influences of the beta(B) antagonist propranolol (PR), the alpha I(AI) antagonist prazosin (PZ), and the alpha 2(A2) antagonist yohimbine (YB) were examined. The induction of TIS1 mRNA by NE was partially blocked by PR or PZ alone, and completely abolished by both antagonists in combination. YB had no effect on TIS1 mRNA expression. These results suggest that NE induces TIS1 mRNA through both B- and A 1-adrenergic, but not A2, pathways. The lack of effect of inhibitors of phospholipase A2 and cyclooxygenase suggests that the A1 component is mediated through a protein kinase C pathway. The induction of transient gene expression by neurotransmitters may mediate the secondary genomic responses and phenotypic changes occurring in astrocytes in response to alterations in neuronal neurotransmitter release.
Arenander
A T
AT
Department of Biological Chemistry, UCLA School of Medicine.
de Vellis
J
J
Herschman
H R
HR
D000818:Animals; D001253:Astrocytes / Q000502:physiology*; D002217:Carbachol / Q000494:pharmacology; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000502:physiology*; D011519:Proto-Oncogenes / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000502:physiology; D011943:Receptors, Adrenergic, beta / Q000502:physiology; D013566:Sympathomimetics / Q000494:pharmacology
D018377:Neurotransmitter Agents; D012333:RNA, Messenger; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D013566:Sympathomimetics; D002217:Carbachol