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34

BRS Physiology

 

 

 

 

 

 

 

 

 

   Signaling Pathways and Mechanisms for Autonomic Receptors

t a b l e

 

  2.2 

 

 

 

 

 

 

Receptor

 

Location

G Protein

Mechanism

 

 

 

 

 

 

Adrenergic

 

 

 

 

 

α1

Smooth muscle

Gq

α2

Gastrointestinal tract

Gi

β1

Heart

Gs

β2

Smooth muscle

Gs

Cholinergic

 

 

IP3 /Ca2+ ↓ cAMP

cAMP

cAMP

NM (N1)

Skeletal muscle

NN (N2)

Autonomic ganglia

M1

CNS

Gq

M2

Heart

Gi

M3

Glands, smooth muscle

Gq

Opening Na+/K+ channels Opening Na+/K+ channels

IP3 /Ca2+ ↓ cAMP

IP3 /Ca2+

IP3 = inositol 1,4,5-triphosphate; cAMP = cyclic adenosine monophosphate.

C.Receptor types in the ANS (Table 2.2)

1.  Adrenergic receptors (adrenoreceptors) a.  a1 Receptors

are located on vascular smooth muscle of the skin and splanchnic regions, the gastrointestinal (GI) and bladder sphincters, and the radial muscle of the iris.

produce excitation (e.g., contraction or constriction).

are equally sensitive to norepinephrine and epinephrine. However, only norepi-

nephrine released from adrenergic neurons is present in high enough concentrations to activate α1 receptors.

Mechanism of action: Gq protein, stimulation of phospholipase C and increase in inositol 1,4,5-triphosphate (IP3) and intracellular [Ca2+].

b.  a2 Receptors

are located on sympathetic postganglionic nerve terminals (autoreceptors), platelets, fat cells, and the walls of the GI tract (heteroreceptors).

often produce inhibition (e.g., relaxation or dilation).

Mechanism of action: Gi protein, inhibition of adenylate cyclase and decrease in cyclic adenosine monophosphate (cAMP).

c.  b1 Receptors

are located in the sinoatrial (SA) node, atrioventricular (AV) node, and ventricular muscle of the heart.

produce excitation (e.g., increased heart rate, increased conduction velocity, increased contractility).

are sensitive to both norepinephrine and epinephrine, and are more sensitive than the α1 receptors.

Mechanism of action: Gs protein, stimulation of adenylate cyclase and increase in cAMP.

d.  b2 Receptors

are located on vascular smooth muscle of skeletal muscle, bronchial smooth muscle, and in the walls of the GI tract and bladder.

produce relaxation (e.g., dilation of vascular smooth muscle, dilation of bronchioles, relaxation of the bladder wall).

are more sensitive to epinephrine than to norepinephrine.

are more sensitive to epinephrine than the α1 receptors.

Mechanism of action: same as for β1 receptors.


 

  Neurophysiology

35

  Chapter 2 

2.  Cholinergic receptors (cholinoreceptors) a.  Nicotinic receptors

are located in the autonomic ganglia (NN) of the sympathetic and parasympathetic nervous systems, at the neuromuscular junction (NM), and in the adrenal medulla (NN). The receptors at these locations are similar, but not identical.

are activated by ACh or nicotine.

produce excitation.

are blocked by ganglionic blockers (e.g., hexamethonium) in the autonomic ganglia, but not at the neuromuscular junction.

Mechanism of action: ACh binds to α subunits of the nicotinic ACh receptor. The nicotinic ACh receptors are also ion channels for Na+ and K+.

b.  Muscarinic receptors

are located in the heart (M2), smooth muscle (M3), and glands (M3).

are inhibitory in the heart (e.g., decreased heart rate, decreased conduction velocity in AV node).

are excitatory in smooth muscle and glands (e.g., increased GI motility, increased secretion).

are activated by ACh and muscarine.

are blocked by atropine.

Mechanism of action:

(1)  Heart SA node: Gi protein, inhibition of adenylate cyclase, which leads to opening of K+ channels, slowing of the rate of spontaneous Phase 4 depolarization, and

decreased heart rate.

(2)  Smooth muscle and glands: Gq protein, stimulation of phospholipase C, and increase in IP3 and intracellular [Ca2+].

3.  Drugs that act on the ANS (Table 2.3)

 

 

 

t a b l e

  2.3 

   Prototypes of Drugs that Affect Autonomic Activity

 

 

 

 

Type of Receptor

Agonist

Antagonist

 

 

 

Adrenergic

 

 

α1

Norepinephrine

Phenoxybenzamine

Phenylephrine

Phentolamine

 

 

 

Prazosin

α2

Clonidine

Yohimbine

β1

Norepinephrine

Propranolol

Isoproterenol

Metoprolol

 

 

Dobutamine

 

β2

Isoproterenol

Propranolol

 

 

Albuterol

Butoxamine

Cholinergic

 

 

Nicotinic

ACh

Curare (neuromuscular

 

 

Nicotine

junction N1

 

 

Carbachol

receptors)

 

 

 

Hexamethonium (ganglionic

 

 

 

N2 receptors)

Muscarinic

ACh

Atropine

 

 

Muscarine

 

 

 

Carbachol

 

ACh = acetylcholine.



36

Brs Physiology

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

t a b l e

 

2.4

 

Effect of the Autonomic Nervous System on Organ Systems

 

 

 

 

 

 

 

 

 

 

 

 

 

 

sympathetic

sympathetic

Parasympathetic

Parasympathetic

organ

 

 

Action

receptor

Action

receptor

 

 

 

 

 

 

 

 

 

Heart

 

 

↑ heart rate

β

 

 

↓ heart rate

M

 

 

 

↑ contractility

β1

 

 

↓ contractility (atria)

M2

 

 

 

↑ AV node conduction

β11

 

 

↓ AV node conduction

M22

Vascular smooth

Constricts blood

α1

 

 

 

muscle

 

 

 

vessels in skin;

 

 

 

 

 

 

 

 

splanchnic

β2

 

 

 

 

 

 

Dilates blood vessels

 

 

 

 

 

 

 

in skeletal muscle

 

 

 

 

 

Gastrointestinal tract

↓ motility

α

, β

 

↑ motility

M

 

 

 

Constricts sphincters

α12

 

2

Relaxes sphincters

M33

Bronchioles

 

 

Dilates bronchiolar

β2

 

 

Constricts bronchiolar

M3

 

 

 

 

smooth muscle

 

 

 

smooth muscle

 

Male sex organs

Ejaculation

α

 

 

Erection

M

Bladder

 

 

Relaxes bladder wall

β

 

 

Contracts bladder wall

M

 

 

 

Constricts sphincter

α21

 

 

Relaxes sphincter

M33

Sweat glands

↑ sweating

M (sympathetic

 

 

 

 

 

 

cholinergic)

 

 

Eye

 

α1

Radial muscle, iris

Dilates pupil (mydriasis)

Circular sphincter

 

muscle, iris

 

β

Ciliary muscle

Dilates (far vision)

Kidney

↑ renin secretion

β1

 

Constricts pupil (miosis)

M

Contracts (near vision)

M

 

Fat cells

↑ lipolysis

β1

AV = atrioventricular; M = muscarinic.

D. effects of the Ans on various organ systems (table 2.4)

e.Autonomic centers—brain stem and hypothalamus

1.medulla

Vasomotor center

Respiratory center

Swallowing, coughing, and vomiting centers

2.Pons

Pneumotaxic center

3.midbrain

Micturition center

4.Hypothalamus

Temperature regulation center

Thirst and food intake regulatory centers

II. sensory systems

A.sensory receptors—general

are specialized epithelial cells or neurons that transduce environmental signals into neural signals.


 

  Neurophysiology

37

  Chapter 2 

The environmental signals that can be detected include mechanical force, light, sound, chemicals, and temperature.

1.  Types of sensory transducers a.  Mechanoreceptors

Pacinian corpuscles

Joint receptors

Stretch receptors in muscle

Hair cells in auditory and vestibular systems

Baroreceptors in carotid sinus

b.  Photoreceptors

Rods and cones of the retina c.  Chemoreceptors

Olfactory receptors

Taste receptors

Osmoreceptors

Carotid body O2 receptors

d.  Extremes of temperature and pain

Nociceptors

2.  Fiber types and conduction velocity (Table 2.5)

3.  Receptive field

is an area of the body that, when stimulated, changes the firing rate of a sensory neuron. If the firing rate of the sensory neuron is increased, the receptive field is excitatory. If the firing rate of the sensory neuron is decreased, the receptive field is inhibitory.

4.  Steps in sensory transduction

a.  Stimulus arrives at the sensory receptor. The stimulus may be a photon of light on the retina, a molecule of NaCl on the tongue, a depression of the skin, and so forth.

b.  Ion channels are opened in the sensory receptor, allowing current to flow.

t a b l e   2.5     Characteristics of Nerve Fiber Types

General Fiber Type

Sensory Fiber Type

 

Conduction

and Example

and Example

Diameter

Velocity

 

 

 

 

A-alpha

Ia

Largest

Fastest

Large α-motoneurons

Muscle spindle afferents

 

 

 

Ib

Largest

Fastest

 

Golgi tendon organs

 

 

A-beta

II

Medium

Medium

Touch, pressure

Secondary afferents of muscle

 

 

 

spindles; touch and pressure

 

 

A-gamma

 

 

γ-Motoneurons to muscle spindles

 

Medium

Medium

(intrafusal fibers)

 

 

 

A-delta

III

Small

Medium

Touch, pressure, temperature,

Touch, pressure, fast pain,

 

 

and pain

and temperature

 

 

B

Small

Medium

Preganglionic autonomic fibers

 

 

 

C

IV

Smallest

Slowest

Slow pain; postganglionic autonomic fibers

Pain and temperature (unmyelinated)