The effects of stress on muscarinic receptors. Heterologous receptor regulation: yes or no?

Abstract

1 Stress is usually comprehended as an event affecting mainly the catecholaminergic system, the hypothalamo-pituitary-adrenocortical (HPA) axis and the receptor systems connected to these neurotransmitters/hormones. Other neurotransmitter/hormone systems can be affected too. Here we review the available data on the effects of different stressful stimuli (physical, chemical, psychological/social, cardiovascular, affecting multiple system) on muscarinic receptors (MR). 2 The data suppose the existence of specific mechanisms that regulate the signalization through MR during different type of stress. 3 Physical stressors (cold vs. heat) reveal opposite type of changes on peripheral-tissue MRs. Chemical stressors (oxidative stress) are tightly connected with MR and it is especially interesting that the sensitivity of MR to oxidative stress is subtype-specific. It is also suggested that heterologous regulation can occur with psychological/social stressors on the organism. Cardiovascular system-disturbing stressors cause imbalance between autonomic receptors or down-regulate MR in the peripheral tissue. Immobilization caused opposite effects on MR in the central nervous system and periphery, where the changes are supposed to be due to heterologous regulation between receptor systems. 4 In conclusion, some data indicate that in specific conditions MR are regulated as a consequence of other changes rather than as a primary effect of stress. On the contrary, in some situations, MR are the first targets to respond to the stress. 5 These findings on stress-induced activity of the cholinergic system and changes in muscarinic receptors support the view that stress is a specific response of the organism.

Effect of Acetylcholine on Mitogen Response of Peripheral Lymphocytes Isolated From Rats Exposed to Chronic Stress

“…However, the overall effect of Ach was smaller and the enhancement in change in IL-2 production by coincubation with Ach was lower in the stress group. This finding is likely due to downregulation of the muscarinic Ach receptors (Myslivecek & Kvetnansky, 2006), an explanation supported by the fact that we observed a decline of the inhibitory effect of atropine in the stress group as compared to the control group. Ach reduced the impact of elevated serum corticosterone on lymphocyte function in the stress group, and this effect was not affected when serum corticosterone concentration increased.…”

Role of corticotropin-releasing factor on bladder function in rats with psychological stress

“…Furthermore, in the hippocampus, the M 2 muscarinic receptor is downregulated in vulnerable rats but upregulated in resilient rats exposed to unavoidable stress 32 . Muscarinic receptors are thought to be the first targets that respond to stress 33 . This response causes changes in organisms and leads to changes in the output system via the main routes: neurons and neuroendocrine systems.…”

Modulation of Muscarinic Signalling in the Central Nervous System by Steroid Hormones and Neurosteroids

“…Prolonged periods of stress-increasing corticosterone reduced ACh uptake and increased the density of mAChRs in the hippocampus [81]. However, it is more likely that the changes in mAChRs expression levels are due to heterologous regulation by different hormones and transmitters [82].…”