AUTONOMIC+NERVOUS+SYSTEM

While sympathetic autonomic //ganglia// are **cholinergic synapses**, post-ganglionic sympathetic nerves are //adrenergic// nerves: They release **norepinephrine** which interacts with **a** **(alpha)** and **b** **(beta)** receptors All adrenergic nerves in the SNS are labeled in **blue**. The **//Somatic (Voluntary)//** Nervous System is also a cholinergic pathway, but unlike the SNS and PNS, it has no ganglia. Instead, **motor neurons** arising in the spinal cord terminate at a specialized synapse in skeletal muscle called the **neuromuscular junction (NMJ)**. This is still a cholinergic synapse because **ACh** is released by the motor neuron, interacts with **nicotinic receptors** and is broken down by **AChE**. nicotinic neuromuscular junction || activates SNS post-ganglionic fibers then PNS post-ganglionic fibers (uses ?) skeletal muscle contraction (used to intensify muscle contractions in myesthenia gravis; as neuromuscular blocking agents) causes muscle relaxation/paralysis || muscarinic urinary bladder smooth muscle heart blood vessels sweat glands salivary glands || increases GI tone/motility (treat constipation) increases urinary bladder tone and motility (treat urine retention) decreases heart rate decreases blood pressure increases sweating increases salivation decrease urinary tone and motility increases heart rate (treat bradycardia) increases blood pressure decreases sweating decreases salivation || [|Go to the Top] **Sympathetic (Adrenergic) Drugs** **RECEPTOR** a1 vasoconstriction (treat hypotension) a2 pre-synaptic membranes in adrenergic nerves || vasoconstriction (treat hypotension) inhibits NE release vasodilates and prevent reflex tachycardia (treat hypertension) || b1 increases heart rate and force (treat heart failure) b2 skeletal muscle arterioles || brochiole dilation (treat asthma etc...) ?? ?? || Type in the content of your new page here.
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 * 1) synthesis of acetylcholine (ACh) from acetyl CoA and choline
 * 2) **storage** of ACh in synaptic vesicles
 * 3) **release** of ACh ( fusion of synaptic vesicle with presysnaptic membrane and release of ACh into the synapse)
 * 4) **action** of ACh by binding to and activating receptors (nicotinic in autonmic ganglia and NMJ and muscarinic in many sites)
 * 5) **inactivation** by enzymatic breakdown of ACh by acetylcholinesterase (AChE) located in the synapse || ||
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 * Cholinergic agonists** are subdivided into **//direct-acting//** and **//indirect-acting//** agonists. **Direct-acting** **agonists** bind to and activate receptors (Fig 2, site 4) at autonomic ganglia (nicotinic), the neuromuscular junction (nicotinic), and a variety of tissues such as the GI tract, heart, exocrine glands (muscarinic). Activation of ganglionic nicotinic receptors leads to activation of SNS pathways following by PNS pathways. This is result of the greater number of post-ganglionic fibers in the SNS (see [|Fig 1]). Thus ganglionic **//agonists//** activate SNS pathways first and **//antagonists//** block SNS responses first. Activation of nicotinic receptors at the NMJ leads to skeletal muscle contraction. Thus **//agonists//** (**//depolarizing neuromuscular blocking agents//**) lead to muscle contraction (followed by paralysis) while **//antagonists//** (**//non-depolarizing neuromuscular blocking agents//**//)// prevent muscle contraction and produce flaccid paralysis. Activation of muscarinic receptors produce 4 responses we're interested in in this class: increased GI tone and motility, increased urinary bladder tone and motility, increased salivation and sweating and decreased heart rate and blood pressure. Thus muscarinic receptor **//agonists//** produce all these responses and can be used to treat non-obstructive constipation and urine retention. They also cause side effects such as diarrhea, drooling and hyperhidrosis, bradycardia and hypotension. **//Antagonists//** produce the opposite effects and can be used to treat diarrhea, to dry up glandular secretions, and increase heart rate while producing side effects such as constipation, dry mouth and tachycardia. **Indirect-acting agonists** produce ACh-like effects by inhibiting the activity of AChE (Fig 2, site 5). Since AChE is the primary way transmission is terminated at //all// cholinergic synapses (see [|Fig 1]), these drugs act at virtually all synapses where ACh is the neurotransmitter (i.e. autonomic ganglia (if they're relatively uncharged), NMJ, and muscarinic receptors)
 * SUMMARY of CHOLINERGIC RECEPTOR ACTION**
 * SUMMARY of CHOLINERGIC RECEPTOR ACTION**
 * autonomic ganglia
 * blocks activation of SNS pos-t ganglionic fibers then PNS fibers (treat hypertension)
 * GI smooth muscle
 * decreases GI tone and motility (treat diarrhea)
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 * Fig 3**
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 * ADRENERGIC SYNAPSE**
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 * 1) synthesis of norepinephrine (NE - not pictured)
 * 2) **storage** of NE in vesicles
 * 3) **release** of NE: fusion of synaptic vesicles with presysnaptic membrane and release of NE into the synapse
 * 4) **action** of NE through binding to and activating receptors (a2 presynaptic and a and b post synaptic)
 * 5) **inactivation** by presynaptic re-uptake transporters (also presynaptic receptors shut off further NE release) || ||
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 * Adrenergic agonists** are sub-divided into 3 classes; **direct-acting**, **indirect-acting** and **dual- acting** agonists.
 * Direct-acting agonists bind to and activate **a1****,** **a2****,** **b1** and **b2** receptors. Fig 3 indicates pre-synaptic a2 receptors and site 4 has a1, a2, b1 and b2 receptors. Naturally -occurring molecules which bind to these receptors include norepinephrine (NE; a neurotransmitter which binds to a1,a2 and b1 receptors), epinephrine (EPI; a hormone produced in and secreted from the adrenal medulla which binds to a1,a2,b1 and b2 receptors -- EPI is a non-selective adrenergic agonist) and dopamine (DA; also a neurotransmitter which binds to DA receptors as well as a1, a2 and b1 receptors ). In addition, the synthetic catecholamine isoproterenol binds to b1 and b2 receptors (it is a non-selective b agonist), but has virtually no effect on a receptors.
 * **Indirect-acting adrenergic agonists** (i.e. amphetamines and cocaine) produce NE-like actions by stimulating NE release (Fig 3 site 3) and preventing its re-uptake (Fig 3 site 5) and thus its inactivation . By preventing NE inactivation, these drugs allow NE to linger in adrenergic synpases. Notice that this is different from the way indirect-acting cholinergic agonists work as they inhibit the activity of AChE, preventing ACh breakdown and allowing it to linger at cholinergic sysnapse.
 * **Dual-acting adrenergic agonists** (i.e. ephedrine) act as a direct- and an indirect-adrenergic agonists (hence dual-acting) - they bind to adrenergic receptors and stimulate NE release. ||
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 * SUMMARY OF ADRENERGIC RECEPTOR ACTION**
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 * SUMMARY OF ADRENERGIC RECEPTOR ACTION**
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 * **LOCATION** ||
 * AGONIST**
 * **ANTAGONIST** ||
 * **ANTAGONIST** ||
 * blood vessels ||
 * vasodilation (treat hypertension) ||
 * blood vessels
 * vasodilation (treat hypertension)
 * heart ||
 * slows heart rate (treat hypertentsion, angina, arrhythmia) ||
 * bronchiole smooth muscle