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PHYSIOLOGY 03028 WEEK 3:

SECOND MESSENGER SYSTEMS; AUTONOMIC NERVOUS SYSTEM

W. Crone (303 FTZ, 629-7439, cronewil@hvcc.edu, http://www.hvcc.edu/academ/faculty/crone/index.html) 2/3/00

Cormack, Ch. 4; Guyton/Hall, Chs. 45, 60; Michael and Rovick, Unit 4; Young/Young, Chs. 1, 18

possible web site (a case study involving the autonomic nervous system):

http://www.healthsci.utas.edu.au/physiol/teaching/organophosphate_poisoning.RP/sld001.htm

 

Binding of the neurotransmitter to its receptor protein to open up ion channels (hence the term, chemically regulated gates). With these opened ion channels, two possibilities:

depolarization:

excitatory postsynaptic potential (EPSP)

hyperpolarization:

inhibitory postsynaptic potential (IPSP)

 

Intracellular signal transduction:1,2

Adenylate cyclase-cAMP second messenger system:

A G-protein is a membrane protein influenced by GTP. Alpha, beta, and gamma subunits may dissociate when a subtance binds with a receptor. One possibility is that the subunit may then bind with adenylate cyclase to form cAMP (cyclic AMP) from ATP. cAMP can then activate a tyrosine kinase to phosphorylate and hence regulate enzyme activity. Phosphodiesterase hydrolyzes cAMP into inaction, so that the second message depends on continued presence of the ligand.

Phospholipase C-Ca2+ second messenger system:

Here, the dissociated G-protein subunit activates the membrane enzyme phospholipase C, which produces, among other things, inositol triphosphate (IP3). IP3 will then diffuse to the ER to trigger a release of Ca2+ from there. Ca2+ binds to calmodulin to activate protein kinases which then phosphorylate other proteins.

Quick overview of autonomic nervous system: (mostly based on Stringer, Ch. 6)3

Cholinergic transmission involves acetylcholine (ACh) as the neurotransmitter, with two types of receptors: nicotinic and muscarinic. Nicotinic receptors are found on postsynaptic nerves (both parasympathetic and sympathetic) and at motor end-plates. Adrenergic transmission involves norepinephrine (NE) as the neurotransmitter, with two types of receptors: a (a 1, a 2), b (b 1, b 2).

The autonomic nervous system (ANS) is responsible for maintaining homeostasis. Two neurons are required to reach from the CNS to the target organ.

These neurons synapse in autonomic ganglia. All preganglionic autonomic neurons release ACh as their neurotransmitter, which binds to nicotinic receptors on the postsynaptic neuron.

Parasympathetic nervous system (vegetative, digestive)

All parasympathetic postganglionic neurons release ACh, which interacts with muscarinic receptors on the target organs. Parasympathetic responses are usually specific and localized.

Sympathetic nervous system (fight or flight)

(Almost) all sympathetic postganglionic neurons release NE, which interacts with either a or b receptors, depending on the target organ. Sympathetic effects tend to be widespread.

 

a 1:

vasoconstriction of arterioles, veins

a 2:

in CNS, decrease NE release (presynaptic) and decrease sympathetic discharge from brain (postsynaptic)

b 1:

specific to heart, increases heart rate and cardiac output

b 2:

smooth muscle relaxation (e.g., bronchus, uterus); vasodilate skeletal/cardiac vessels.

Two sympathetic nervous system quirks:

  1. postganglionic sympathetic neurons that have sweat (cooling, not smelly apocrine) glands as target organs release ACh, with the sweat glands having muscarinic receptors.
  2. The adrenal medullary cells are, in effect, modified postganglionic neurons, and when stimulated, they release NE & epinephrine (adrenaline) (1:4 ratio). Note that NE is a > b 1 > > b 2 and epinephrine a @ b (b 1 and b 2) in terms of receptor effect.

Many organs are innervated by both sympathetic and parasympathetic neurons, which usually have opposing effects. In the resting state, most organs are under parasympathetic control, while in a fight-or-flight response, sympathetic control takes precedence.

exception: vascular smooth muscle is only innervated by sympathetic fibers, so that blood pressure is always under sympathetic control.

So how do nicotinic, muscarinic, and adrenergic receptors work?1

nicotinic:

ACh binds to the receptor, directly opening up a channel that allows influx of Na+

muscarinic:

ACh binds to the receptor, stimulating a G-protein to dissociate into subunits. The a subunit or the b g complex can then bind to an ion channel.

alpha-adrenergic:

a 1 receptor binding stimulates the cell via the Ca2+ second messenger system. a 2 receptor binding blocks cAMP production in contrast.

beta-adrenergic:

b 1 and b 2 stimulate via the cAMP second messenger system.

 

  1. SI Fox, Human Physiology, 6th ed. (WCB McGraw-Hill, Boston, 1999), pp. 167-170, 227, 294-298.
  2. AC Guyton and JE Hall, Textbook of Medical Physiology, 9th ed. (WB Saunders, Philadelphia, 1996), pp. 571, 930.
  3. JL Stringer, Basic Concepts in Pharmacology (McGraw-Hill, New York, 1996), pp. 37-46.

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Please send comments and questions to: cronewil@hvcc.edu

 

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This web page last updated on February 3, 2000