Functional Characterization of α9-Containing Cholinergic Nicotinic Receptors in the Rat Adrenal Medulla: Implication in Stress-Induced Functional Plasticity

Abstract

An increase in circulating adrenal catecholamine levels constitutes one of the mechanisms whereby organisms cope with stress. Accordingly, stimulus-secretion coupling within the stressed adrenal medullary tissue undergoes persistent remodeling. In particular, cholinergic synaptic neurotransmission between splanchnic nerve terminals and chromaffin cells is upregulated in stressed rats. Since synaptic transmission is mainly supported by activation of postsynaptic neuronal acetylcholine nicotinic receptors (nAChRs), we focused our study on the role of ␣9-containing nAChRs, which have been recently described in chromaffin cells. Taking advantage of their specific blockade by the ␣-conotoxin RgIA (␣-RgIA), we unveil novel functional roles for these receptors in the stimulus-secretion coupling of the medulla. First, we show that in rat acute adrenal slices, ␣9-containing nAChRs codistribute with synaptophysin and significantly contribute to EPSCs. Second, we show that these receptors are involved in the tonic inhibitory control exerted by cholinergic activity on gap junctional coupling between chromaffin cells, as evidenced by an increased Lucifer yellow diffusion within the medulla in ␣-RgIA-treated slices. Third, we unexpectedly found that ␣9-containing nAChRs dominantly (Ͼ70%) contribute to acetylcholine-induced current in cold-stressed rats, whereas ␣3 nAChRs are the main contributing channels in unstressed animals. Consistently, expression levels of ␣9 nAChR transcript and protein are overexpressed in cold-stressed rats. As a functional relevance, we propose that upregulation of ␣9-containing nAChR channels and ensuing dominant contribution in cholinergic signaling may be one of the mechanisms whereby adrenal medullary tissue appropriately adapts to increased splanchnic nerve electrical discharges occurring in stressful situations.

Intra-accumbal and Peripheral administration of nicotine reduces the side-effects of Inescapable Stress

“…In line with previous studies, our results have shown that inescapable stress causes widespread alterations in animal performance, including reduced body weight loss, brain weight, food intake, increased anorexia and water intake and adrenal gland weight (McEwen, 2007;Colomer et al, 2010;G Hunter, 2012;Guérineau et al, 2012;Lutfy et al, 2012). It would be renowned that according to preceding studies, stress stimulates HPA axis and upsurges secretion of epinephrine and glucocorticoids from the central and cortical parts of the adrenal gland, respectively (McEwen, 2007; B Hunter et al, 2010).…”

“…It would be renowned that according to preceding studies, stress stimulates HPA axis and upsurges secretion of epinephrine and glucocorticoids from the central and cortical parts of the adrenal gland, respectively (McEwen, 2007; B Hunter et al, 2010). It has been reported that the reduced level of dopamine in the nucleus accumbens recovers the animal's ability to acquire used to stress following inescapable stress (Dubrovsky, 2005;Viveros et al, 2007;Colomer and Olivos-Oré et al, 2010;Hunter and Bloss et al, 2010). Various parts of reward system are involved in the variation of stress responses and the nucleus accumbens as a main parts of this reward system, acting a vital role in inhibiting the effects of stress (Zhao et al, 2007).…”

Molecular Interaction of α-Conotoxin RgIA with the Rat α9α10 Nicotinic Acetylcholine Receptor

“…In addition to the auditory system, transcripts and/or protein for a9 and a10 subunits have been found in lymphocytes, skin keratinocytes, sperm, dorsal root ganglion, sympathetic neurons, macrophages, and adrenal chromaffin cells (Nguyen et al, 2000;Lustig et al, 2001;Lips et al, 2002;Haberberger et al, 2004;Kurzen et al, 2004;Peng et al, 2004;Kumar and Meizel, 2005;Colomer et al, 2010;Simard et al, 2013). The physiologic role of a9a10 nAChRs in the auditory system has been determined through studies done with a9 and a10 knockout mice (Vetter et al, 1999(Vetter et al, , 2007.…”

Cloning, synthesis, and characterization of αO-conotoxin GeXIVA, a potent α9α10 nicotinic acetylcholine receptor antagonist

“…More recently, α9α10 nAChRs have been found in adrenal chromaffin cells, where they may modulate responses to stress (7). In addition, transcripts for the α9 and/or α10 subunit have been reported in a variety of nonneuronal cells, including immune cells.…”