Function
The autonomic nervous system is responsible for maintaining the homeostatic environment of the body with adjustments affecting major organ systems such as neuronal, circulatory, respiratory, integumentary, digestive, and urinary. The autonomic nervous system divides into sympathetic, parasympathetic, and enteric divisions.[9] Within the parasympathetic and sympathetic nervous system, neurons are categorized as preganglionic and postganglionic, depending on the location of their cell bodies within the central or peripheral nervous systems. The N2 or neuronal nicotinic receptor subtype exists on all postganglionic cell bodies. The N2 receptors are responsive to acetylcholine and transmit signals from the preganglionic to the postganglionic cell.[9] The ionic flux generated at the postganglionic cell is responsible for excitatory signal transduction to effector organs of the autonomic nervous system. Separately, the N1 or muscle nicotinic receptor is at the neuromuscular junction on muscle cells generating voluntary muscle movement.[10] An excitatory signal may become generated through N1 receptor activation. Depending on the strength of the signal, receptor activation may result in membrane depolarization with subsequent muscle contraction.
Muscarinic receptors mediate many functions of the parasympathetic nervous system. The muscarinic receptors are on various organs throughout the body. Receptors diffusely express on organs of the neuronal, cardiac, musculoskeletal, pulmonary, digestive, and urinary systems. As mentioned, different receptor subtypes exist on different organs, producing various effects. The overall function of the receptors aims to achieve the “rest and digest” function of the parasympathetic nervous system. While the sympathetic nervous system readies the body for “fight or flight,” the parasympathetic nervous system functions as the unconscious restorative and energy-conserving system. Therefore, many functions of muscarinic receptors may be referred to as opposing the action of the sympathetic nervous system. Receptors present on cardiac muscle cells receive innervation from the vagus nerve and act to slow the heart rate and decrease the force of contraction. Receptors function at the SA node, AV node, atria, and within the ventricles, resulting in a slowed heart rate, decreased conduction velocity, and a prolonged cardiac muscle refractory period.[11]
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Within the digestive system, receptor activation stimulates intestinal motility and digestive enzyme secretion. Receptor activation in the lungs leads to smooth muscle contraction, narrowing the airways, and increasing secretion production. Furthermore, muscarinic receptors are present throughout the central nervous system and have demonstrated important functions in both learning and memory. Animal models lacking the M1 receptor develop deficiencies in both cognition and long-term potentiation.[12] Therefore the activation of M1 receptors serves to maintain synaptic plasticity and neuronal differentiation.[5] The wide range of actions mediated by muscarinic receptors highlights their critical role within the autonomic nervous system. With such a diffuse presence of receptors, medical therapies activating or blocking the receptor can cause a range of effects beyond the targeted use.
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