Sunday, March 1, 2015
15 ANS NEUROTRANSMITTERS AND RECEPTORS
AND RECEPTORS
- Based on the neurotransmitter they produce and release, autonomic neurons are classified as either
- cholinergic or
- adrenergic.
- are integral membrane proteins located in the plasma membrane of the postsynaptic neuron or effector cell.
Cholinergic Neurons and Receptors
- Cholinergic neurons (ko¯ -lin-ER-jik) release the neurotransmitter acetylcholine (ACh).
- In the ANS, the cholinergic neurons include
(2) sympathetic postganglionic neurons that innervate most sweat glands, and
(3) all parasympathetic postganglionic neurons
- ACh is stored in synaptic vesicles and released by exocytosis.
- It then diffuses across the synaptic cleft and
- binds with specific cholinergic receptors, integral membrane proteins in the postsynaptic plasma membrane.
- The two types of cholinergic receptors, both of which bind ACh, are
- nicotinic receptors
- and muscarinic receptors.
Nicotinic receptors
- are present in the plasma membrane of dendrites and cell bodies of both sympathetic and parasympathetic postganglionic neurons ,
- the plasma membranes of chromaffin cells of the adrenal medullae,
- and in the motor end plate at the neuromuscular junction.
- They are so named because nicotine mimics the action of ACh by binding to these receptors.
- (Nicotine, a natural substance in tobacco leaves, is not a naturally occurring substance in humans and is not normally present in nonsmokers.)
Muscarinic receptors
- are present in the plasma membranes of all effectors (smooth muscle, cardiac muscle, and glands)
- innervated by parasympathetic postganglionic axons.
- In addition, most sweat glands receive their innervation from cholinergic sympathetic postganglionic neurons
- and possess muscarinic receptors.
- These receptors are so named because a mushroom poison called muscarine mimics the actions of ACh by binding to them.
- Nicotine does not activate muscarinic receptors, and
- muscarine does not activate nicotinic receptors,
- but ACh does activate both types of cholinergic receptors.
Activation of nicotinic receptors by ACh
- causes depolarization
- and thus excitation of the postsynaptic cell, which can be a postganglionic neuron, an autonomic effector, or a skeletal muscle fiber.
Activation of muscarinic receptors by ACh sometimes
- causes depolarization (excitation) and
- sometimes causes hyperpolarization (inhibition), depending on which particular cell bears the muscarinic receptors.
- binding of ACh to muscarinic receptors inhibits (relaxes) smooth muscle sphincters in the gastrointestinal tract.
- ACh excites muscarinic receptors in smooth muscle fibers in the circular muscles of the iris of the eye, causing them to contract.
- Because acetylcholineis quickly inactivated by the enzyme acetylcholinesterase (AChE), effects triggered by cholinergic neurons are brief.
Adrenergic Neurons and Receptors
- In the ANS, adrenergic neurons (ad -ren-ER-jik) release norepinephrine (NE), also known as noradrenalin.
- Most sympathetic postganglionic neurons are adrenergic.
- Like ACh, NE is synthesized and stored in synaptic vesicles and
- released by exocytosis.
- Molecules of NE diffuse across the synaptic cleft
- and bind to specific adrenergic receptors on the postsynaptic membrane,
- causing either excitation or inhibition of the effector cell.
- Adrenergic receptors bind both norepinephrine and epinephrine.
The norepinephrine can be
- either released as a neurotransmitter by sympathetic postganglionic neurons
- or released as a hormone into the blood by chromaffin cells of the adrenal medullae; epinephrine is released as a hormone.
- The two main types of adrenergic receptors are
- alpha (α ) receptors and
- beta( β) receptors, which are found on visceral effectors innervated by most sympathetic postganglionic axons.
- These receptors are further classified into subtypes—α 1,α 2, β 1,β2, andβ3—based on the specific responses they elicit and by their selective binding of drugs that activate or block them.
- activation of α1 and β 1 receptors generally produces excitation,
- and activation of α2 andβ2 receptors causes inhibition of effector tissues.
- β 3 receptors are present only on cells of brown adipose tissue, where their activation causes thermogenesis (heat production).
- Cells of most effectors contain either alpha or beta receptors;
- some visceral effector cells contain both.
- Norepinephrine stimulates alpha receptors more strongly than beta receptors;
- epinephrine is a potent stimulator of both alpha and beta receptors.
The activity of norepinephrine at a synapse is terminated
- either when the NE is taken up by the axon that released it
- or when the NE is enzymatically inactivated by either
- catechol-O-methyltransferase (COMT)
- or monoamine oxidase (MAO).
- Compared to ACh, norepinephrine lingers in the synaptic cleft for a longer time.
- Thus, effects triggered by adrenergic neurons typically are longer lasting than those triggered by cholinergic neurons.
Location and Responses of Adrenergic and Cholinergic Receptors | ||
TYPE OF RECEPTOR | MAJOR LOCATIONS | EFFECTS OF RECEPTOR ACTIVATION |
Cholinergic | Integral proteins in postsynaptic plasma membranes; activated by the neurotransmitter acetylcholine. | |
Nicotinic | Plasma membrane of postganglionic sympathetic and parasympathetic neurons. Chromaffin cells of adrenal medullae. Sarcolemma of skeletal muscle fibers (motor end plate). | Excitation → impulses in postganglionic neurons. Epinephrine and norepinephrine secretion. Excitation → contraction |
Muscarinic | Effectors innervated by parasympathetic postganglionic neurons Sweat glands innervated by cholinergic sympathetic postganglionic neurons. Skeletal muscle blood vessels innervated by cholinergic sympathetic postganglionic neurons | In some receptors, excitation; in others, inhibition. Increased sweating. Inhibition → relaxation → vasodilation. |
Adrenergic | Integral proteins in postsynaptic plasma membranes; activated by the neurotransmitter norepinephrine, and by the hormones norepinephrine and epinephrine. | |
α1 | Smooth muscle fibers in blood vessels that serve salivary glands, skin, mucosal membranes, kidneys, and abdominal viscera; radial muscle in iris of eye; sphincter muscles of stomach and urinary bladder. Salivary gland cells. Sweat glands on palms and soles. | Excitation → contraction, which causes vasoconstriction, dilation of pupil, and closing of sphincters. Secretion of K+ and water. Increased sweating |
α2 | Smooth muscle fibers in some blood vessels Cells of pancreatic islets that secrete the hormone insulin (beta cells). Pancreatic acinar cells. Platelets in blood. | Inhibition → relaxation → vasodilation. Decreased insulin secretion. Inhibition of digestive enzyme secretion. Aggregation to form platelet plug. |
β1 | Cardiac muscle fibers. Juxtaglomerular cells of kidneys. Posterior pituitary. Adipose cells. | Excitation → increased force and rate of contraction. Renin secretion. Secretion of antidiuretic hormone. Breakdown of triglycerides → release of fatty acids into blood |
β2 | Smooth muscle in walls of airways; in blood vessels that serve the heart, skeletal muscle, adipose tissue, and liver; and in walls of visceral organs, such as the urinary bladder. Ciliary muscle in eye. Hepatocytes in liver. | Inhibition → relaxation, which causes dilation of airways, vasodilation, and relaxation of organ walls. Inhibition → relaxation. Glycogenolysis (breakdown of glycogen into glucose). |
β3 | Brown adipose tissue. | Thermogenesis (heat production). |
Receptor Agonists and Antagonists
A large variety of drugs and natural products can selectively activate or block specific cholinergic or adrenergic receptors.
- An agonist is a substance that binds to and activates a receptor, in the process mimicking the effect of a natural neurotransmitter or hormone.
- an adrenergic agonist at 1 receptors,
- is a common ingredient in cold and sinus medications.
- Because it constricts blood vessels in the nasal mucosa,
- phenylephrine reduces production of mucus,
- thus relieving nasal congestion.
- is a substance that binds to and blocks a receptor,
- thereby preventing a natural neurotransmitter or hormone from exerting its effect.
atropine
- blocks muscarinic ACh receptors,
- dilates the pupils,
- reduces glandular secretions,
- and relaxes smooth muscle in the gastrointestinal tract.
- As a result,
- it is used to dilate the pupils during eye examinations,
- in the treatment of smooth muscle disorders such as iritis and intestinal hypermotility,
- and as an antidote for chemical warfare agents that inactivate acetylcholinesterase.
- often is prescribed for patients with hypertension (high blood pressure).
- It is a nonselective beta blocker,
- meaning it binds to all types of beta receptors and
- prevents their activation by epinephrine and norepinephrine.
due to its blockade of 1 receptors—namely,
- decreased heart rate
- and force of contraction
- and a consequent decrease in blood pressure.
- due to blockade of 2 receptors may include
- hypoglycemia (low blood glucose),
- resulting from decreased glycogen breakdown
- and decreased gluconeogenesis (the conversion of a noncarbohydrate into glucose in the liver),
- and mild bronchoconstriction (narrowing of the airways).
- If these side effects pose a threat to the patient, a selective 1 blocker such as metoprolol (Lopressor®) can be prescribed instead of propranolol.
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