Intercellular Chemical Messages

1
Intercellular Chemical Messages

• Nor-epinephrine, Cholecystokinin (CCK), and
  Histamine

2
Problem/Question

• Nor-epinephrine, CCK, and Histamines have
  multiple actions related to various target cell
  receptors
• Know as a neurotransmitter, GI hormone, and
  paracrine, respectively, all have other functions
  as well
• We will classify them and describe their actions
  as well as provide an example of a drug that
  either mimics or blocks the effects of the
  chemical messages

3
Nor-epinephrine

• Is a neurotransmitter when released by a neuron
  into the synapse
• Is a hormone when released into the blood by the
  Adrenal Medulla
• Sends chemical messages to many different target
  tissues
• Smooth muscle
• Cardiac muscle
• Endocrine and exocrine glands
• Adipose Tissue

4
Neurotransmitter Release in the Synapse

• At synapses in the CNS, nor-epinephrine affects
  the part of the brain where impulsivity and
  attention are controlled
• This also effects the Fight or Flight Response
  during stress
• Binds to adrenergic receptors on target cells

5
Hormone Secretion From the Adrenal Medulla

• A stressful stimulus causes acetylcholine release
  from pre-ganglionic sympathetic fibers
  innervating the medulla
• This stimulates the release of Nor-epinephrine
  into the blood where it is carried to adrenergic
  receptors on various visceral target tissues
• Nor-epinephrine (NE) secreted as a hormone into
  the blood intensifies and prolongs the responses
  caused by NE released as a neurotransmitter from
  sympathetic postganglionic axons.

6
Alpha (a) Receptors

• At a1 receptors, NE causes smooth muscle
  contraction of the arterioles (Vasoconstriction)
• During the Fight or Flight response
  vasoconstriction helps blood go only where it is
  needed (skeletal muscles, liver, and heart) and
  diverts it from the GI tract where it is not
  needed
• At a2 receptors, NE causes the smooth muscle of
  the GI tract to relax and decreases pancreatic
  secretions

7
Beta (ß) Receptors

• At ß1 receptors, NE causes increased heart rate,
  and therefore blood pressure

8
Propranolol ß antagonist

• Drug used for angina pectoris (chest pain) and
  cardiac arrhythmias (abnormal heart rate)
  hypertension (high blood pressure)
• A non-specific ß -Blocker which binds to both
  types of ß receptors and prevents their
  activation by Nor-epinephrine
• The effects of Propranolol are decreased heart
  rate and force of contraction which decreases
  blood pressure

9
Cholecystokinin (CCK)

• Intestinal hormone
• Secreted by the duodenum, and
• causes the release of digestive
• enzymes and bile form the
• pancreas and gallbladder, respectively
• Help to digest fat, protein and carbohydrate,
  aids in their digestion and absorption

10
Cholecystokinin

• Also acts as a neurotransmitter in the brain
• Mediates satiety by acting on the receptors
  distributed widely throughout the central nervous
  system
• Decreases the desire to eat by giving you a
  feeling of fullness
• CCK administration significantly reduces hunger
  in adult male rats

11
Satietrol

• A powder drink mix supplement with
• main ingredient of potatoes also containing the
  milk-derived protein glycomacropeptide
• Used as a meal replacement, low calorie snack, or
  as a drink prior to eating it stimulates the
  release of CCK
• Shown to speed up the digestive process and
  decrease hunger, helping in weight loss

12
What is Histamine?

• Histamine literally means a vasoactive amine
  made up of histidine residues
• It is a paracrine released by damaged cells that
  acts on the cells in its immediate vicinity
• It is also a protein involved in allergic
  reactions and acts as a neurotransmitter in the
  sleep-wake cycle

13
What does it do?

• Inflammatory response
• Directly
• Upon the release of histamine by the mast cell,
  the permeability of the nearby vessels increases.
  
• This leads to the movement of blood fluids into
  the area which leads to swelling (edema).
• Indirectly
• Histamine can also trigger a response by other
  leukocytes in the area which leads to
  inflammation.

14
What does it do?

• Allergic response
• A normally harmless substance (i.e. pollen) comes
  in contact with lymphocytes (mast cells) specific
  for that substance (antigen).
• This results in the release of histamine into the
  surrounding tissues.
• Sleep-Wake Cycle
• Histamine seems to have an arousal effect on
  the brain and when histamine is released in the
  brain, wakefulness occurs.

15
Drugs that block the messages?

• Antihistamines
• drugs that inhibit the response associated with
  histamine
• Anti-histamines often have a drowsiness effect
  and this can be explained by histamines role in
  wakefulness.
• Claritin
• Claritin results in the neutralization of
  histamine which prevents it from binding and
  activating immune-related cells in the area.

16
Analogy