Lecture 6: Chemical Messengers

Intercellular communication

Cells communicating with each other

Types of Intercellular Communication

1. Direct

2. Indirect

Direct Intercellular Communication

Gap junctions: pores (formed from → connexons) connecting adjacent cells together

Ex: cardiac muscle

“Sharing same cytoplasm, ions, and communicating fast with one another”

Indirect Intercellular Communication

Chemical messengers

Classification of Chemical Messengers

1. Functional

   1. “How it’s functioning”

2. Chemical Properties

   1. “usually lipophilic or lipophobic aka nonpolar or polar”

3. Chemical Class

   1. “5 different chemical classes”

Functional Classifications

1. Paracrines

2. Neurotransmitters

3. Hormones

Paracrines

Chemicals that communicate with neighboring cells (cells that are very close not directly attached) (tissue level)

Distance: short

Mode of transportation: diffusion (high → low conc.)

Includes:

Autocrines: chemicals that act on the same cell that secreted them

Examples of Paracrines

1. Growth factors

2. Clotting factors

3. Cytokines

   1. “Chemical messengers that are essential for a lot of different immune responses”

Neurotransmitters

Chemicals released by neurons → synapse (connection site between) → target cell

“Neuron Anatomy: Axon and Soma. Released @ Axon Terminal”

Distance: short

Mode of transportation: diffusion

Example of Neurotransmitter

Acetylcholine

• “Major autonomic neurotransmitters”

Hormones

Chemicals released from endocrine glands, or neurosecretory neuron → ISF → blood

• Neurosecretory neuron: a neuron that releases hormones

• ISF: interstitial fluid = fluid between cells

Distance: long

Mode of transportation: blood

Chemical Properties Classifications

1. Lipophilic

2. Lipophobic

Lipophilic

Lipid soluble

Acts on receptors inside the cell

• “lipid loving”

• “nonpolar” = no trouble crossing membrane so receptors are inside cell

• “doesn’t mix well w/water b/c fats don’t mix well with water”

Lipophobic

Usually water soluble

Acts on receptors on the cell membrane

• “lipid fearing”

• “polar” = hard to cross membrane

Chemical Classes

1. Amino acids

2. Amines (modified aa’s)

3. Peptide and proteins (chains of aa’s)

4. Steroids

5. Eicosanoids

Amino Acids

Basic monomer for proteins

• “building block for proteins”

• “Proteins mix well w/water b/c they are polar”

Chemical property: lipophobic

Functional classification: neurotransmitter (NT)

Examples of Amino Acids

Glutamate

• “Excitatory neurotransmitter”

Aspartate

• “Excitatory neurotransmitter”

Glycine

• “Inhibitory”

GABA

• “Inhibitory”

Amines

Derived from amino acids

Contains -NH2 group

Chemical property: lipophobic (except thyroid hormones)

Functional classification: Paracrine, NT, and hormones

Examples of Amines

1. Dopamine

   1. “elicits feeling of reward”

2. Serotonin

   1. “Happiness”

3. Norepinephrine and Epinephrine

   1. “fight or flight sympathetic NS response”

   2. “can even bond to same type of receptor”

   3. Norep: used more like NT

   4. Epi: used more like hormone

4. Histamine

   1. “Local immune response like bug bite”

5. Thyroid hormones

   1. “metabolism increases if you increase thyroid hormones”

Peptides and Proteins

Chain of amino acids

Most common

Chemical property: lipophobic

Functional classification: paracrine, NT, and hormones

Examples of Peptides and Proteins

1. Cytokines

   1. “chemical messengers used in your immune response”

2. Variety of NT and Hormones

Steroids

Derived from cholesterol

• “example of a lipid”

Chemical property: lipophilic

• “cuts through membrane, receptor for steroids is inside the cell”

Functional classification: hormones

• “will travel thru blood”

Examples of Steroids

1. Testosterone

2. Cortisol

   1. “stress hormone”

3. Aldosterone

   1. “increases BP”

4. Progesterone

Eicosanoids (type of lipid)

Derived from arachidonic acid (fatty acid)

• “fatty acid derived from phospholipid”

Chemical property: lipophilic

• “Non-polar, so cuts through the membrane, receptor likely inside the cell”

Functional classification: Paracrine

Examples of Eicosanoids

1. Prostaglandins

   1. “helps perceive pain”

2. Prostacyclins, Thromboxanes, and Leukotrienes

   1. “associated w/blood and blood clotting”

Signal Transduction Mechanism

1. Source releases a ligand (chemical messenger)

2. Travels to target cell

   1. “could be by diffusion, by blood, long or short distances”

3. Ligand binds to receptors on/in target cell → functional change

   1. “has to do with chemical property of chemical messenger (lipophilic [in] or lipophobic [on])”

Properties of Cell Receptors

1. Messenger specific

2. Multiple receptors types present on/in a cell

3. The more interactions (between messengers and receptors) → the greater the effect

Factors affecting interactions between messengers and receptors

1. Messenger concentration

   1. “increased concentration = more interactions”

2. # of receptors

   1. “more = higher likelihood of bonding to a particular messenger”

3. Affinity

   1. “how much does that receptor want to bind to that chemical messenger?”

Intracellular Mediated Response

Receptors: inside cell

Messenger: lipophilic

• “Has to cut thru membrane”

Response: gene activation or inhibition

• “activate or inhibit DNA”

Effects of Intracellular Mediated Response

1. Slow → Protein synthesis takes time

2. Long-lasting → Proteins last a while

Membrane Receptor Mediated Response

Receptors: on membrane

Messenger: lipophobic

• “Can’t cut thru membrane”

Categories of Membrane Receptor Mediated Response

1. Channel-linked

   1. “receptor is linked to a channel”

2. Enzyme-linked

   1. “receptor is linked to a specific enzyme”

3. G protein-linked

   1. “receptor linked to a G protein”

Channel-linked Receptor

Receptor also acts as a (protein) channel

Response: opens channels in membrane

Enzyme-linked Receptor

Receptor also acts as an intracellular enzyme

• “enzyme that functions inside the cell”

Response: activates enzyme

G protein-linked Receptor

Receptor is linked to a group of proteins (G group) in membrane

Response: activates G protein (“moves laterally in membrane, away from receptor”) → activates another membrane bound protein (“could be a channel or enzyme, etc.”)

*Can activate multiple enzymes from one messenger because lots of G groups can be attached to receptor “amplifying the signal”

• Reference picture on Slide 37 of Chemical Messengers Lecture

Second Messengers

Intracellular molecule produced (“made inside cell”) / entered (“entered inside the cell”) as a response to an extracellular messenger (1st chemical messenger)

CAN AMPLIFY SIGNAL

Examples of Second Messengers

1. Ca²⁺

2. Cyclic AMP (cAMP)

Long Distance Communication

Required to regulate all body activities

Regulated by:

1. Endocrine system

2. Nervous system

Endocrine System Regulation of Long Distance Communication

1. Releases hormones into blood

2. Effects moderately slow

   1. “limited by speed of blood circulation”

Nervous System Regulation of Long Distance Communication

1. Signal target cells through NT

2. Effects fast (1/100 of a second)

Amines…

A) are only NT

• “aa’s”

B) are only hormones

• “steroids”

C) are only paracrines

• “eicosanoids”

D) can be all of the above

• “also peptides and proteins”
  

Which of the following is a paracrine?

A) Thromboxanes

• “type of eicosanoid, helps w/blood clotting”

B) Glutamate

• “NT b/c aa”

C) Cortisol

• “stress hormone, example of steroid”

D) GABA

• “NT b/c aa”

Which of the following chemical messengers will bind to an intracellular receptor?

A) Glycine

• “aa = lipophobic”

B) Norepinephrine

• “amines = lipophobic except thyroid hormones”

C) Testosterone

• “steroid = lipophilic, derived from cholesterol”

D) Seratonin

• “amines = lipophobic except thyroid hormones"

*looking at chemical property for this question, looking for lipophilic (can pass thru membrane)

A membrane receptor mediated response…

A) directly results in transcription of a gene

• “intracellular mediated response”

B) can result in G protein activation

C) is generally slow to take into effect

• “intracellular mediated response b/c creating protein, transcription/translation”

D) would occur with prostacyclins

• “example of eicosanoids = lipophilic”

Which of the following is not true of G proteins?

A) are associated with membrane bound receptors

B) will act on a cytoplasmic protein when activated

• “will actually act on another membrane bound protein”

C) can trigger a second messenger cascade

D) All of the above