Activation of pirenzepine-sensitive muscarinic receptors induces a specific pattern of immediate-early gene expression in rat brain neurons.
Accumulating evidence suggests that immediate-early gene transcription factors such as c-Fos, form part of an intracellular signalling pathway linking the activation of neuronal receptors by neurotransmitters to changes in neuronal gene expression. Recently it has been demonstrated that the centrally active muscarinic receptor agonist pilocarpine induces both c-fos mRNA and protein in rat brain. In this report using immunocytochemical and in situ hybridization techniques we demonstrate for the first time that in addition to c-fos, pilocarpine administration increases the neuronal expression of jun-B, krox-20 and krox-24 (zif-268) but not related c-jun and jun-D genes in rat cortex and hippocampus. Pretreatment of animals with atropine or pirenzepine significantly reduced induction of c-fos, jun-B, krox-20 and krox-24 genes in both hippocampus and cortex. These results show that activation of pirenzepine-sensitive muscarinic receptors results in a specific pattern of immediate-early gene expression in rat brain neurons. We suggest that the combinatorial complexity of immediate-early gene induction may allow receptor-specific control of gene expression in vivo.
Department of Pharmacology and Clinical Pharmacology, School of Medicine, University of Auckland, New Zealand.
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Hughes
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Dragunow
D000818:Animals; D001921:Brain / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D051766:Early Growth Response Protein 1; D051767:Early Growth Response Protein 2; D005786:Gene Expression Regulation / Q000187:drug effects*; D017781:Genes, Immediate-Early / Q000187:drug effects / Q000502:physiology*; D016762:Genes, fos / Q000187:drug effects; D016758:Genes, jun / Q000187:drug effects; D006624:Hippocampus / Q000378:metabolism; D017874:Immediate-Early Proteins; D017403:In Situ Hybridization; D007700:Kinetics; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D010424:Pentobarbital / Q000494:pharmacology; D010862:Pilocarpine / Q000494:pharmacology; D010890:Pirenzepine / Q000494:pharmacology*; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis; D016755:Proto-Oncogene Proteins c-jun / Q000096:biosynthesis; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000502:physiology*; D012016:Reference Values; D013997:Time Factors; D014157:Transcription Factors / Q000096:biosynthesis; D015533:Transcriptional Activation
D004268:DNA-Binding Proteins; D051766:Early Growth Response Protein 1; D051767:Early Growth Response Protein 2; C486110:Egr1 protein, rat; C497328:Egr2 protein, rat; D017874:Immediate-Early Proteins; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D011976:Receptors, Muscarinic; D014157:Transcription Factors; D010862:Pilocarpine; D010890:Pirenzepine; D010424:Pentobarbital