NT’s, Receptors and their actions

• Cholinergic Receptors (receptors that respond to Ach)– Nicotinic – Muscarinic

• Adrenergic Receptors (receptors that respond to NE)– Alpha– Beta

Other NT

Dopamine, serotonin, GABA, Glutimate

• Binding of NT to receptors on post synaptic membrane can cause EPSPs or IPSPs depending on the combination of NT and receptor at any given synapse.

Acetylcholine (ACh)

Used extensively in PNS and in restricted areas of CNS

Broken down by Achase

Two types of receptors

1. Nicotinic

2. muscarinic

•Autonomic ganglia,•Neuromuscular junctions•Post ganglionic Parasympathetic neurons

Nicotinic (Cholinergic) Receptors — Activated by ACh:

• Ionotropic: activation directly leads to movement of ions across membrane

• Chemical (ligand) gated channels

ACh bind receptors/gated channel channel opens Na+ flows in depolarization

• Excitation (EPSP)

Fig. 7.27 Muscarinic (Cholinergic) Receptors—Activated by ACh:

• Metabotropic: binding of receptors directly leads to chemical reactions (metabolism)

• Activates a second-messenger; G-protiens

ACh binds receptor G protien is activated G protien signals gated channel next step varies

• If G protien opens K+ channels: ↑ K+ outflow hyperpolarization IPSP

• If G protein closes Ca+ or Na+ channels: ↓ Ca+/Na+ flow into cell hyperpolarization IPSP

• if G protein closes (blocks) K+ channels: ↓ K+ leaking depolarization EPSP

Can also close K+

channel in other cases

Fig. 9.11

Or reduce Ca+ inflow

Norepinephrine (NE) and Epinephrine (E)

• Monoamine > catecholamine

• broken down by monoamine oxidases (MOA)

• Used in sympathetic post-ganglionic neurons and in some CNS areas.

Fig. 7.31 Adrenergic Receptors (NE, E)

•Metabotropic; binding of receptor initiates metabolic reactions

NE binds receptor G-protein activates adenylate cyclase cAMP kinase open/closes channel (and/or intracellular effects) IPSP or EPSP

or epinephrine

And/or activates proteins within the cytoplasm, and/or initiates events in the nucleus

Changes in nucleus

Fig. 9.1

Fig. 9.7

Fig. 9.10

muscarinic

e.g., smooth muscle effects, increases digestive activity, slow heart rate , gland secretion

Receptor Type Neurotransmitter Sensativity

Effector Effect on Effector

Nicotinic Ach Skeletal muscle, adrenal medulla, post-gangioloic neurons of ANS

Excitatory

Muscarinic Ach in PD-ANS Cardiac muscle, smooth muscle, exocrine glands, some endocrine glands

Excitatory or inhibitory

Alpha-1 Norepinephrine > epinephrine

Most sympathetic target tissues

excitatory

Alpha-2 Norepinephrine > epinephrine

Digestive organs inhibitory

Beta-1 Norepinephrine = epinephrine

Heart excitatory

Beta-2 Epinephrine only Smooth muscle of arterioles and bronchioles

Inhibitory (i.e., leads to dilation)

Table 7.5

CASTOR BEANS

CASTOR BEANS

MMHow various substances influence neuron and synaptic function

• Review of ANS neurons and NT’s

Dopamine

• In CNS• Can be excitatory or inhibitory• 2 major dopamine systems in brain

– Involved with motor control (involved with inhibiting muscles that should be relaxed/preventing overstimulation of skeletal muscle)

• Basal Nuclei (nigrostriatal system)

– involved in behavior and emotional reward (“feel good” NT)• Part of reward system that influences behavior (“is it worth it to

choose a course of action)• Most addictions activate this system, also risk taking behaviors• Overactivity contributes to schizophrenia

– Which is treated by anti-dopamine drugs

• Mesolimbic dopamine system7-67

Serotonin • In CNS (and enteric system/GI tract)• Excitatory and inhibitory• Involved in regulation of mood, behavior, appetite and cerebral

circulation, muscle control, bone remodelling, reproductive behavior.

• Effects mood, perception, and behavior– Linked to depression

• LSD is structurally similar• Ecstasy targets serotonin receptors• SSRIs (serotonin-specific reuptake inhibitors) are antidepressants

– e.g., Prozac, Zoloft, Paxil, Luvox– Block reuptake of serotonin, prolonging its action

7-66

GABA (gamma-aminobutyric acid)

• Inhibitory (opens Cl- channels) • is most common NT in brain• Inhibits neural pathways (so they are not over-

active)• Linked to anxiety levels (increased GABA

reduces axiety)• Barbituates & Benzodiazepines (Xanax and

valium) are agonists of GABA receptors• Alcohol also targets GABA receptors

7-69

Glutamate

• Glutamate most important excitatory NT in CNS• Important in memory formation and learning• Involved with excitotoxicity

7-69

Glycine

• Inhibitory (mostly within brainstem and spinal cord)

• Important in maintiaing proper balance of inhibition and excitation that controls skeletal muscle contraction– Opens Cl- channels which hyperpolarize– Strychnine blocks glycine receptors

• Causes spastic paralysis (over active stimulation/excitation of skeletal muscle)

7-69

• Interesting concept—NOT fact checked