title: IFNγ Increases M2 Muscarinic Receptor Expression in Cultured Sympathetic Neurons.
abstract: M2 muscarinic receptors are expressed on both parasympathetic and sympathetic nerve endings where they function as autoinhibitory receptors to limit release of acetylcholine and norepinephrine, respectively. M2 muscarinic receptor expression on parasympathetic nerves is decreased by viral infection and by gamma-interferon (IFNγ) and increased by dexamethasone; and these effects are of clinical relevance in the etiology and treatment of asthma. Whether IFNγ and dexamethasone similarly modulate M2 receptor expression on sympathetic nerves is not known. To address this question, we examined the effects of IFNγ and dexamethasone on M2 receptor expression at the mRNA and protein level in primary cultures of sympathetic neurons dissociated from the rat superior cervical ganglia (SCG). Semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) indicated that neither IFNγ nor dexamethasone altered M2 receptor transcript levels. However, western blot analyses demonstrated that IFNγ, but not dexamethasone, increases M2 receptor protein expression in sympathetic neurons. Increased expression did not significantly alter subcellular localization of M2 receptors in sympathetic neurons as determined using immunocytochemistry. These findings indicate that M2 receptors are differentially regulated in different types of autonomic neurons, and they suggest a novel mechanism by which IFNγ may contribute to airway hyperreactivity in viral-induced asthma.
authors.affiliation: Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, CA, USA.
authors.forename: Ana Cristina G
authors.initials: AC
authors.lastname: Grodzki
authors.forename: Atefeh
authors.initials: A
authors.lastname: Ghogha
authors.forename: Linley
authors.initials: L
authors.lastname: Mangini
authors.forename: Allison D
authors.initials: AD
authors.lastname: Fryer
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Lein