Nicotinic receptor Alpha7 expression during mouse adrenal gland development.

Lorise C Gahring,Sierra Palumbos,Scott W Rogers,Elizabeth Myers

doi:10.1371/journal.pone.0103861

Abstract

The nicotinic acetylcholine receptor alpha 7 (α7) is a ligand-activated ion channel that contributes to a diversity of cellular processes involved in development, neurotransmission and inflammation. In this report the expression of α7 was examined in the mouse developing and adult adrenal gland that expresses a green fluorescent protein (GFP) reporter as a bi-cistronic extension of the endogenous α7 transcript (α7G). At embryonic day 12.5 (E12.5) α7G expression was associated with the suprarenal ganglion and precursor cells of the adrenal gland. The α7G cells are catecholaminergic chromaffin cells as reflected by their progressive increase in the co-expression of tyrosine hydroxylase (TH) and dopamine-beta-hydroxylase (DBH) that is complete by E18.5. In the adult, α7G expression is limited to a subset of chromaffin cells in the adrenal medulla that cluster near the border with the adrenal cortex. These chromaffin cells co-express α7G, TH and DBH, but they lack phenylethanolamine N-methyltransferase (PNMT) consistent with only norepinephrine (NE) synthesis. These cell groups appear to be preferentially innervated by pre-ganglionic afferents identified by the neurotrophin receptor p75. No afferents identified by beta-III tubulin, neurofilament proteins or p75 co-expressed α7G. Occasional α7G cells in the pre-E14.5 embryos express neuronal markers consistent with intrinsic ganglion cells and in the adult some α7G cells co-express glutamic acid decarboxylase. The transient expression of α7 during adrenal gland development and its prominent co-expression by a subset of NE chromaffin cells in the adult suggests that the α7 receptor contributes to multiple aspects of adrenal gland development and function that persist into adulthood.

Highlights

Nicotinic acetylcholine receptors are expressed and participate in the normal physiological functions of many neuronal and non-neuronal cell processes
The a7 receptor is distinguished from other Nicotinic acetylcholine receptors (nAChR) because it can function as a homomeric receptor composed of five-identical subunits, it has an exceptionally high permeability to calcium, and in addition to the endogenous ligand acetylcholine or the addictive substance in tobacco products nicotine, it is fully activated by choline [3]
The immune-staining pattern for a7G becomes more restricted in the adult adrenal gland where anti-green fluorescent protein (GFP) primary antibody immune-staining signal is restricted to groups of cells that are largely localized to the perimeter of the adrenal medulla cortex and adjacent to the inner boundary of the adrenal cortex (Fig. 1C)

Summary

Introduction

Nicotinic acetylcholine receptors (nAChR) are expressed and participate in the normal physiological functions of many neuronal and non-neuronal cell processes. The expression of a7 by peripheral catecholaminergic sympathetic systems has been suggested to include chromaffin cells of the adrenal gland [15,17,18,19], and chromaffin cellbased expression libraries provided the starting material that contributed to the discovery of this and other clones encoding nicotinic acetylcholine receptor (nAChR) subunits (see [3]) Many of these receptor subunits are expressed in both developing and adult adrenal structures, but reports of the status of a7 expression in the adult has been less clear and often contradictory [20,21,22]. This includes modulation of vesicular release from these adrenal cells [24,25,26], the identity and distribution of a7 expression in this organ requires further clarification

Methods

Results

Conclusion