Nicotine regulates nicotinic cholinergic receptors and subunit rnRNAs in PC 12 cells through protein kinase A

Thelma C. Madhok, Shannon G. Matta, Burt Sharp

Research output: Contribution to journalArticle

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Abstract

To understand the up-regulation of neuronal nicotinic cholinergic receptors (nAcChRs) that results from chronic in vivo treatment with nicotine, we studied the effect of nicotine on [3H]nicotine binding sites on PC 12 cells. PC 12 cells were grown in nicotine hemisulfate (10-6 to 10-3 M) or vehicle for 7 days, and specific [3H]nicotine binding was measured. Nicotine (10-6 to 10-4 M) dose-dependently increased specific binding by up to 2.6-fold over basal levels in 5-7 days, whereas a 10-3 M concentration failed to do so. In contrast, [3H]nicotine binding to PC 12 cell mutants (A126.1132 and A123.7), deficient in CAMP-responsive protein kinase A Types I and/or II, was unaffected by nicotine. Northern gel analysis of nAcChR subunit mRNAs from wild type PC 12 cells showed that the mRNA encoding the dominant agonist-binding subunit, α3, was significantly reduced by nicotine, as early as 4 h after treatment, whereas mRNA for the structural β2 subunit was slightly increased. In contrast, the a3 subunit mRNA from the PC 12 cell mutant A123.7 was not significantly decreased after 4 h and 7 days of nicotine treatment. These studies indicate that nicotine up-regulates expression of nAcChRs on wild type PC 12 cells and reduces the content of α3 subunit mRNA; these effects require an intact protein kinase A system. The divergent effects of nicotine on the nAcChR compared to its α3 subunit mRNA suggests that enhanced expression of nicotinic receptors may not involve synthesis of new receptor subunit proteins.

Original languageEnglish (US)
Pages (from-to)143-150
Number of pages8
JournalMolecular Brain Research
Volume32
Issue number1
DOIs
StatePublished - Jan 1 1995

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Nicotinic Receptors
Cholinergic Receptors
Cyclic AMP-Dependent Protein Kinases
Nicotine
Messenger RNA
Up-Regulation
Protein Subunits
Gels
Binding Sites

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cellular and Molecular Neuroscience

Cite this

Nicotine regulates nicotinic cholinergic receptors and subunit rnRNAs in PC 12 cells through protein kinase A. / Madhok, Thelma C.; Matta, Shannon G.; Sharp, Burt.

In: Molecular Brain Research, Vol. 32, No. 1, 01.01.1995, p. 143-150.

Research output: Contribution to journalArticle

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