Structure and Function of the parasympathetic Nervous System

Muscarinic receptors

Cholinergic, Classic agonist are Muscarine

• Natural product found in some mushrooms

• Subtypes 1-5

Nicotinic receptors

Cholinergic, Classic agonist: Nicotine

• Natural alkaloid most commonly found in tobacco

  • Subtypes N_N, N_M

Pilocarpine

Classic cholinergic muscarinic receptor agonist, increases salivation with shoguns’ disease, autoimmune disease that reduces salivation, and some glaucoma.

Lobeline

Synthetic version of nicotine, used for treatment of nicotine use disorder.

Muscarinic receptors types

G-protein-coupled receptors

Nicotinic receptor types

Ligand gated receptors

Nicotinic receptor - ligand-gated receptors

• Acetylcholine binds to the extracellular part of the cell

• Conformational change （depolarize the channel）

• Causing sodium influx and causing effects

Nicotinic receptor - N_N

• N stands for neuron - located in ganglion

• Neuronal type, ganglion receptors

• Found most commonly on postganglionic nerve cells

N_N receptor mechanisms

• Pre-ganglion fiber, meet up with a second order neuron

• Second order neuron use acetylcholine across the synapse to propagate that signal to the tissue.

• Nerve tissue uses nicotinic type acetylcholine receptors to send that signal

• Causing conformational change in the ligand-gated channel

  • Sodium influx, depolarized and send the signal down.

N_M receptors

• M is for muscle

  • Not part of the parasympathetic nervous system

Muscarinic - M1 receptor

• G_q/11 coupled receptors

• IP3-DAG cascade

• Has stimulatory effect

M₁ receptor distribution and effect

• Brain - greeted cognition and memory

• Stomach: release HCl and pepsinogen (precursor to pepsin - break down proteins to amino acids)

M₂ receptor

• G_i/_o coupled receptors. When there is i, think about inhibitory

• Inhibition of cAMP （second messenger）, activation of K channels

  • Oppose of beta 1 effects (instead of 4 increase, here is 4 decrease)

M₂ receptor distribution and effects

• Majority on heart

  • SA node: decrease rhythmicity (rate), chronotropic

  • Atria: decrease contractility (force), inotropic

  • AV node: decrease velocity, dromotropic; increase refractory period

  • Ventricles: small decrease in contractility (force), inotropic

These are compensatory when baroreceptor reflexes - receptors that cause compensation when certain vital sign is too high

M₃ receptor

Effects are smooth muscle or skeletal muscle contraction, contraction often leads to secretion

• G_q/₁₁ coupled receptors

• IP₃ and DAG cascade

• Stimulatory effect

M₃ receptor distribution and effects in glands

Majority on glands - for secretion

• Lacrimal - tear secretion

• Saliva - saliva secretion

• Bronchiolar - secretion in the lungs, decongestants can oppose that

• Pancreas - digestive enzymes secretions (resting and digesting - secrete more enzymes that break down food)

• Enzymes - secretion of insulin

  • GI - secretion of mucus

M₃ receptor distribution and effect on smooth muscle

• Iris contraction

• Ciliary body: Lens （accomodation）

• Bronchial: Bronchoconstriction - smooth muscle contraction, when you are resting, you want it to constrict

• GIT: Peristalsis

• Bladder: Detrusor muscle contraction

  • Trigone and sphincter: relaxation

M₄ and M₅

• They are located in the CNS

  • Hippocampus

  • Substantia nigra

• less well characterized

• May play a role in certain neurological diseases

these are cholinergic receptors and they are in the CNS - brain

Smooth muscle contraction

When smooth muscle contracts, blood vessels also contracts causing vasoconstriction

Cholinergic side effects

Constipation, blurred vision, and urinary retention, also dry skin, dry mouth.