Cholinergic regulation of the rat adrenal zona glomerulosa

Abstract

Using histochemical and immunocytochemical methods, cholinergic nerve fibres were demonstrated in the rat adrenal cortex, primarily in the capsule and zona glomerulosa, and in the medulla. Some terminated among the glomerulosa cells or around blood vessels. Occasional fibres were also seen in the fasciculata, ending in islets of chromaffin tissue without ramifications on cortical cells.To clarify the role of cholinergic innervation, a microvolume perifusion system was used to study steroid production by the rat adrenal capsule-glomerulosa. Acetylcholine (ACh) itself had no reproducible effects; however, since variable amounts of endogenous ACh were present, the actions of antagonists were also studied. The M 1 muscarinic receptor antagonist pirenzepine (10 and 100 µM) stimulated aldosterone secretion. This stimulation was abolished by co-incubation with carbachol, the M 1 agonist McN A-343 and by atropine. We found that the action of pirenzepine was blocked by nifedipine (Ca 2+ channel blocker), suggesting that pirenzepine (through release of endogenous ACh) provides an acute stimulus by enhancing Ca 2+ inflow. Hemicholine, a choline uptake blocker, reduced the stimulatory effect of pirenzepine on steroid secretion, confirming that stimulation was of neural origin. Neither the non-selective muscarinic receptor antagonist atropine, the selective M 1 -M 3 muscarinic receptor antagonist 4-DAMP, nor the selective M 2 muscarinic receptor antagonist methoctramine influenced aldosterone output. Receptor-binding studies revealed the existence of M 3 receptors in capsule-glomerulosa homogenates. We conclude that pirenzepine acts on presynaptic M 1 autoreceptors to increase spontaneous ACh release from varicose axon terminals that lie in close proximity to the glomerulosa cells. In turn ACh may thus stimulate steroidogenesis acutely through M 3 receptors. These results support the concept of a direct cholinergic influence on zona glomerulosa function in the rat.

Endogenous ouabain-like factor (OLF) secretion is modulated by nicotinic mechanisms in rat adrenocortical cells

“…Previously we reported the presence of an extended peripheral cholinergic network in the zona glomerulosa of rat adrenal cortex (Jánossy et al, 1998). Cholinergic nerve fibres terminating in this area are the physiological source of OLF secretagogue, and ACh released from the nerve endings exerts a direct neuronal modulation on steroidogenesis in ZG cells.…”

“…Cholinergic nerve fibres terminating in this area are the physiological source of OLF secretagogue, and ACh released from the nerve endings exerts a direct neuronal modulation on steroidogenesis in ZG cells. For example, muscarinic regulation of cortisol and aldosterone, both in bovine adrenocortical cells (Benyamina et al, 1987;Kojima et al, 1986;Rubin and Warner, 1975) and in perfusion of rat adrenal capsule-glomerulosa preparations (Jánossy et al, 1998), has been reported. Nicotinic modulation of steroidogenesis in cat and rat adrenocortical cells (Skowronski and Feldman, 1994;Barbieri et al, 1989) and the influence of nicotine on the secretion of other steroids has also been reported (Skowronski and Feldman, 1994;Kasson and Hsueh, 1985;Patterson et al, 1990).…”

“…In a previous study addressing the role of cholinergic mechanisms in steroid secretion by rat ZG and ZFR cells (Jánossy et al, 1998), the possibility arose that acetylcholine (ACh) may influence the production of aldosterone. In the present study we hypothesized that OLF secretion is also regulated, at least in part, by ACh.…”

Expression and localization of pChAT as a novel method to study cholinergic innervation of rat adrenal gland

“…The adrenal medulla receives a most dense nerve supply terminating on the postganglionic neurons and chromaffin cells (Kondo et al, 1985;Kesse et al, 1988). However, the adrenal cortex is also innervated, especially in the outer capsule and z. glomerulosa region (Watanabe et al, 1990;Janossy et al, 1998). Medullary neurons in the mammalian adrenal gland have been shown not only to innervate medullary chromaffin cells, but also to project to the cortex, approaching secretory cells and blood vessels.…”

“…The presence of cholinergic nerve fibers in the adrenal glands has been studied in rat (Purwar, 1978;Parker et al, 1993;Janossy et al, 1998;Murabayashi et al, 2009), mouse (Oomori et al, 2013), guinea pig (Parker et al, 1990), cow (De Diego, 2010, goat (Watanabe et al, 1990), pig (Tornøe et al, 2000), and human (Charlton et al, 1991) using different markers. Additionally the vagal innervation of the adrenal gland of guinea pig and rat (Coupland et al, 1989;Tomlinson and Coupland, 1990) and the observation of AChE-positive neurons of rat adrenal medulla (Coupland and Holmes, 1958;Coupland, 1965a;Tomlinson and Coupland, 1990) support the localization of cholinergic nerve fibers in the adrenal glands.…”