Histamine Definitions Flashcards
occupation of a single receptor by an antagonist interferes with the response of the agonist.
Antagonism
occupation of a single receptor by an agonist leads to a response.
Agonism
A molecule that induces antagonism. Removes the effect of the agonist.
Antagonist
A molecule that induces an effect (induces agonism).
Agonist
discovered the biological effects of histamine. Won the Nobel prize in 1936 for medicine + physiology. Received a Studentship from the Victorian novelist, George Eliot.
Sir Henry Hallett Dale
George Eliot
Created the Lewes Studentship that was awarded to Sir Henry Hallett Dale.
Imidazole Ring
A ring (structure) that exists on histamine. It contains two nitrogens.
Histidine
An amino acid. The non-toxic form of histamine. Has an amine group and a carboxyl group attached to a central carbon.
Histidine Decarboxylase
Removes the carboxyl group from histidine (decarboxylates). This produces an amine (histamine) and CO2. This is found intracellular in the cytoplasm.
Mast Cells
Ubiquitous cells. Have granules that contain histamine and other things.
Ubiquitous
Coming in many different forms and present in a number of tissues.
Basophil
a type of white blood cell. The least common type of granulocyte, representing only about 0.5 - 1% of circulatory white blood cells. Contains histamine.
Enterochromaffin-like Cells
Communicate in paracrine fashion. Contain histamine that when released plays a major role in stimulating gastric secretion. Found in the gastric mucosa.
Gastric Mucosa
The mucous layer in the stomach.
Heparin
another molecule found in the granules of Mast Cells. Naturally ocuring glycosaminoglycan. Part of its function is aiding in growth and repair in cells.
Glycosaminoglycan
widespread function including growth and repair in cells.
Prostaglandins
found in the granules of Mast Cells. Involved in dealing with injury and illness.
ATPase
an enzyme found in granular membrane that transports protons into the cell to create a proton motor force.
VMAT2
an anti-port that exchanges one proton for one histamine.
Anti-port
Exchanges one proton for one hydrophilic cation.
Mediators
other things held within the granule: ATP, heparin, prostaglandins.
Antigens
any substance that causes your immune system to produce antibodies against it.
Antibodies
proteins generated by our immune system in response to antibodies to fight against infectious agents.
Serotonin
a chemical signalling molecule. Known to cause satisfaction, happiness, and optimism in CNS. Also has many other functions.
Leukotrienes
Causes tightening of airway muscles and the production of excess mucus and fluid.
Translocation
the first step of degranulation
Fusion
the final step of degranulation
Docking
the second step of degranulation
Vasodilation
the dilation of veins, occurs as a result of histamine affection venous cells.
Edema
Fluid accumulation (occurs when stung by a bee), occurs as a result of histamine affecting vasculature.
Endogenous
From within the organism / cell.
Exogenous
From outside the organism / cell
ECL Cells
Enterochromaffin-like cells.
PMF
proton motor force
VMAT2
Vesicular monoamide transporter 2
CNS
Central Nervous System
Histamine
Example of a messenger molecule. Basophils, mast cells, neurons, and Enterochomaffin-like cells
ATPase
transports protons from cytosol into the granule to create the proton motive force
Proton Motive Force
ATPase creates a concentration gradient (more protons inside granule than in cytosol) which supports the transport mechanism VMAT2
VMAT2
uses the proton gradient to swap a proton with a histamine molecule (going inside a granule). VMAT2 is an antiport which means it moves two molecules or ions in opposite directions between a membrane
Release
Activation/ degranulation caused by physical/chemical stimulii. Release has a 3 step process: Translocation, docking and fusion
H1
smooth muscle, endothelium, brain
H2
Gastric Mucosa, Cardia muscle, Mast cells, brian
H3
brain, neurons
H4
Immune cells
Affinity
Potency (x axis); ability to bind to receptor
Efficacy
ability to elicit a response; doability
EC50
concentration required to elicit a 50% response, measure of affinity
AJ Clark and Occupancy Model
Drugs occupy receptors; response is proportional to receptor occupation; one molecule= one receptor= one unit response; always more drug molecules than receptors available
Kon
ability to get on the receptor (how fast molecules access receptors)
Koff
how long molecules stay bound (major contributor to affinity)
KD
concentration required to saturate half of the receptors=Koff/Kon
KA
1/KD= ffinity of the receptor
Logand Binding is…
Stochastic
Agonist
elicits a response
Antagonist
does NOT elicit response
Pharmacological antagonism
antagonism on a single receptor
Orphan receptors
are waiting to have ligand identified
De-orphanized receptors
ligand of the receptor is identified
Competitve antagonist=
surmountable
Irreversible antagonist=
non-surmountable antagonism; cannot be washed out and decreases max response