1. Muscarinic receptors on blood vessels

2. Some pre-synaptic receptors

Nicotinic: ligand-gated Na⁺/K⁺ channels

1. N_N = found in autonomic ganglia. (N_G)

2. N_M = found in neuromuscular junctions

Muscarinic: GPCR that act through 2^nd messengers

1. M₁ = enteric system, CNS

2. M₂ = Heart

3. M₃ = smooth muscle, glands & endothelium

4. M₄ = CNS?

5. M₅ = CNS?

Nicotinic: ligand-gated Na⁺/K⁺ channels

1. N_N = found in autonomic ganglia. (N_G)

1. Ion channel --> depolarization --> action potential

2. N_M = found in neuromuscular junctions

1. Ion channel --> depolarization --> action potential

Muscarinic: GPCR that act through 2^nd messengers

1. M₁ = Gq-coupled: increase IP₃ and DAG

2. M₂ = G_i-coupled: decrease cAMP, activate K⁺ channels

3. M₃ = Gq-coupled: increase IP₃ and DAG

4. M₄ = CNS?

5. M₅ = CNS?

Location (M₁) = myenteric plexus

***Sympathetic ganglia and ADRENAL MEDULLA!!!

Can be activated by McN-A-343 and blocked by pirenzipine!!!!

Action (M₁) = Parasympathetic activation of enteric nervous system

Location (M₂) = heart

Action (M₂) = decrease HR and decrease contractiblilty of atria

Location (M₃) = smooth muscle, glands, endothelium

Action (M₃) =

1. Increase exocrine gland secretion (sweat, gastric acid)

2. Increase gut peristalsis

3. Increase bladder contraction

4. Bronchoconstriction

5. Increase pupillary sphincter/contractor muscle contraction (miosis)

6. Ciliary muscle contraction (accomodation)

7. Not directly PS: DILATION of blood vessels ***Through Endothelium Derived Relaxing Factor (EDRF) and nitric oxide (NO)

Alpha Receptors:

1. Alpha₁ = G_q --> Increase IP₃ and DAG --> Increases Ca²⁺ --> contraction/secretion

2. Alpha₂ = G_i --> Decrease cAMP --> decrease transmitter release & causes contraction (somehow)

Beta Receptors:

1. Beta₁ = G_s --> increase cAMP --> increase HR, contraction force, and renin release

2. Beta₂ = G_s --> increase cAMP --> relax smooth muscle, increase glycogenolysis, increase HR & force

3. Beta₃ = G_s --> increase cAMP --> increase lipolysis

Dopamine:

1. D₁ = G_s --> increase cAMP --> renal vascular smooth muscle

Alpha Receptors:

1. Alpha₁ =

     1. Most vascular smooth muscle (contracts)

     2. Pupillary dilator muscle (contracts - mydriasis)

     3. Pilomotor smooth muscle (contracts - erects)

     4. Liver (stimulates glycogenolysis)

2. Alpha₂ =

     1. Neuron endplate (inhibits NE release)

     2. Some vascular smooth muscle (contracts)

     3. Platelets (stimulates aggregation)

     4. Fat cells (inhibition of lipolysis)

     5. Pancreatic B cells (inhibits insulin release)

3. Nonspecific:

     1. GI --> smooth muscle relaxation

     2. Prostate in men --> smooth muscle relaxation

     3. Bladder trigone and sphincter --> increase sphincter tone, relax bladder

Beta Receptors:

1. Beta₁ =

     1. Heart (stimulates rate and force)

     2. Juxtaglomerular cells (stimulates renin release)

2. Beta₂ =

     1. Airways, uterine & vascular SM (relaxation)

     2. Liver (stimulates glycogenolysis)

     3. Pancreatic B cells (stimulates insulin release)

     4. Somatic motor neuron terminals (causes tremor)

     5. Heart (stimulates rate and force)

3. Beta₃ =

     1. Fat cells (stimulates lipolysis)

Dopamine Receptors:

1. D₁ =

     1. Renal and other splachnic vessels (dilates --> decreases resistance)

2. D₂ =

     1. Nerve terminals (inhibits adenylyl cyclase)

Aqueous humor production:

Flow: Ciliary process (posterior chamber) → anterior chamber → trabecular network (canal of Schlemm)

*β₁-adrenergic receptors increase production

1. β₁-adrenergic antagonists block AH production

2. Carbonic anhydrase inhibitors block AH production

3. α₂ agonists (apraclonidine): decrease AH production; also increase uveoscleral drainage

Uveoscleral Flow:

1. α₂ agonists (apraclonidine): decrease AH production; also increase uveoscleral drainage?

2. Prostaglandin agonists PGF_2α (latanoprost): als increase uveoscleral drainage

3. α agonists (epinephrine): increase uveoscleral flow

Trabecular Tone:

1. Muscarinic agonists (carbachol, pilocarpine) cause miosis → incresed trabecular tone & porosity

2. Acetylchoinesterase inhibitors (physostigmine, echothiophate) cause miosis → incresed trabecular tone & porosity

Osmotic:

1. Mannitol: removal of H₂O from eye

Notes:

1. Miosis (constriction) → ↑ trabecular tone & porosity → ↑ drainage

*M₃ receptors on pupillary sphincter

2. Mydriasis (dilation) → ↓ trabecular tone & porosity → ↓ drainage

*α₁-agonists are on pupillary dilator muscle

3. Cycloplegia (accomodation) → Muscarininc receptors

Parasympathetic:

1. Deep breathing

2. Valsalva maneuver

Sympathetic:

1. Tilt table (orthostatic hypotension)

2. valsalva

3. Sudomotor:

- SSR: Sympathetic Skin Response for sweating (not very sensitive)

- QSART: Sudomotor Axon reflex test (gold standard

  - specific for postganglionic fiber loss and small unmyelinated fibers

Other:

1. Control of catecholamine metabolism