L6 The parasympathetic nervous system and cholinergic neurotransmission

Stimulation of the PNS is more organ specific, with discrete innervation. Ganglia are [blank_start]closer[blank_end] to the organs. Parasympathetic pre-ganglionic nerve endings release [blank_start]ACh[blank_end], which acts on [blank_start]nicotinic[blank_end] receptors. This is the [blank_start]same[blank_end] as the sympathetic pre-ganglionic nerve endings. Post-ganglionic nerve endings release ACh which acts on [blank_start]muscarinic[blank_end] receptors. This is [blank_start]different[blank_end] to the sympathetic post-ganglionic nerves as they release [blank_start]catecholamines[blank_end] to act on [blank_start]adrenergic[blank_end] receptors. Remember, muscarinic receptors give slower [blank_start]physiological[blank_end] responses.

Muscarinic receptors are G-protein coupled. Select the muscarinic receptors which have excitatory effects through IP3, instead of inhibitory effects through cAMP.

M1 receptors are [blank_start]neural[blank_end], and found in the autonomic and enteric [blank_start]ganglia[blank_end], gastric [blank_start]cells[blank_end], and [blank_start]cerebral[blank_end] cortex. M2 receptors are cardiac, found in the [blank_start]SA and AV nodes[blank_end]. M3 receptors are glandular and smooth muscular innervating, and are found in [blank_start]exocrine[blank_end] glands, smooth muscle ([blank_start]GIT, eye, airways, bladder[blank_end]) and blood [blank_start]vessels[blank_end]. M4 and M5 are within the [blank_start]CNS[blank_end] only.

Organ specific actions of the PNS: Heart, via M2 stimulation: • [blank_start]decreased[blank_end] SA node firing • [blank_start]decreased[blank_end] AV node conduction • [blank_start]decreased[blank_end] heart rate, contractility, and CO Lungs, via M3 stimulation • [blank_start]constrict[blank_end] bronchial muscle • [blank_start]increase[blank_end] secretions • [blank_start]decrease[blank_end] airway diameter Bladder, via M3 and M2 stimulation • [blank_start]Contraction[blank_end] of detrusor • [blank_start]Relax[blank_end] sphincter • Micturition reflex These effects are opposite to the SNS.

Muscarinic agonists mimic the action of [blank_start]ACh[blank_end] at muscarinic receptors. They are agonists at [blank_start]both[blank_end] nicotinic and muscarinic receptors, but more potent at [blank_start]muscarinic[blank_end] receptors. They have [blank_start]few[blank_end] important clinical uses, but the treatment of [blank_start]glaucoma[blank_end] is one of them. M agonists [blank_start]constrict[blank_end] the ciliary muscle for better [blank_start]drainage[blank_end] in the eye, to [blank_start]reduce[blank_end] pressure.

Muscarinic antagonists are [blank_start]parasympatholytic[blank_end] drugs and [blank_start]competitive[blank_end] antagonists. All muscarinic antagonists show similar [blank_start]peripheral[blank_end] effects. CNS effects, [blank_start]excitatory[blank_end] and seen especially in children, include restlessness, agitation, hyperactivity, and hyperthermia (from no [blank_start]sweating[blank_end]).

Cholinesterase inhibitors inhibit [blank_start]cholinesterases[blank_end] from degrading and recycling [blank_start]acetylcholine[blank_end], and therefore increase ACh, enhancing cholinergic [blank_start]neurotransmission[blank_end]. They inhibit acetylcholinesterase (AChE) and plasma/butylcholinesterases about equally. Anticholinergic toxidrome (unwanted [blank_start]side effects[blank_end] at therapeutic dose) includes mental [blank_start]confusion[blank_end], mydriasis(pupil [blank_start]dilation[blank_end] causing poor eyesight), flushed skin, dry skin, and dry mucous membranes.