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

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.