Introduction to Autacoids Flashcards
Define autacoids.
These are endogenous substances with complex physiologic and pathophysiologic functions. They have potent nonautonomic pharmacologic effects when administered as drugs. Examples include: histamine, serotonin, bradykinin and prostaglandins.
Compare and contrast autacoids and endocrine hormones in terms of source.
Autacoids are produced by many cells in the body, whereas endocrine hormones are released from a single endocrine gland.
Compare and contrast autacoids and endocrine hormones in terms of mode of action.
Autacoids are usually produced by local cells and operate in the immediate vicinity as local hormones to convey information from one cell to another, whereas endocrine hormones circulate in the blood to affect ‘target’ tissues, usually found distant from the site of production.
Compare and contrast autacoids and endocrine hormones in terms of duration of action.
Autacoids have short half-lives, whereas endocrine hormones have longer half-lives.
List four categories of autacoids.
(1) Biologically active amines
(2) Eicosanoids
(3) Cytokines
(4) Vasoactive (endogenous) peptides:
✔ Vasoconstrictor peptides
✔ Vasodilator peptides
List two biologically active amines.
Histamine, Serotonin
List three eicosanoids.
Prostaglandins, Leukotrienes, Thromboxanes
List the vasoconstrictor and vasodilator vasoactive peptides.
Vasoconstrictor peptides: angiotensin II, vasopressin, endothelins, neuropeptide Y, urotensin
Vasodilator peptides: bradykinin & related kinins, natriuretic peptides, vasoactive intestinal peptide, substance P, neurotesin, calcitonin gene-related peptide, adrenomedullin
Briefly outline functions of histamine.
(1) It is a mediator of inflammation.
(2) it stimulates the production of gastric acid in the stomach by binding to H2 receptors on parietal cells.
(3) Histamine acts as a neurotransmitter in the brain, where it plays a role in regulating sleep-wake cycles, appetite, and cognitive functions.
(4) In the respiratory system, histamine can cause constriction of the bronchioles, which is a significant factor in asthma and other respiratory conditions.
Briefly discuss synthesis of histamine.
It is formed by the decarboxylation of the amino acid L-histidine.
Enzyme: histidine decarboxylase
Where is histamine sequestered in the human body?
Most tissue histamine is sequestered and bound in granules in mast cells or basophils.
Where is non-mast cell histamine found?
(1) In the brain, where it functions as a neurotransmitter.
(2) In the enterochromaffin-like (ECL) cells of the fundus of the stomach. [ECL cells release histamine, one of the primary gastric acid secretagogues, to activate the acid-producing parietal cells of the mucosa.]
Briefly discuss storage & metabolism of histamine.
✔ Once formed, histamine is either stored or rapidly inactivated.
✔ Very little histamine is excreted unchanged.
✔ Histamine is metabolized by the enzymes monoamine oxidase (MAO) & diamine oxidase.
✔ It is converted to N-methylhistamine, methylimidazoleacetic acid, and imidazoleacetic acid (IAA).
List 4 neoplasms that are associated with increased numbers of mast cells or basophils and with increased excretion of histamine and its metabolites.
◾ Systemic mastocytosis
◾ Urticaria pigmentosa
◾ Gastric carcinoid, &
◾ Occasionally myelogenous leukemia
How can excess produciton of histamine in the body be detected?
This can be detected by its major metabolite, imidazole acetic acid, in the urine;
What stimuli may cause release of histamine from tissues?
✔ Destruction of cells as a result of cold
✔ Toxins from organisms
✔ Venoms from insects and spiders &
✔ Trauma
List two general mechanisms by which histamine is released from mast cells.
◾ Immunologic release
◾ Chemical and mechanical release
Briefly discuss immunological release of histamine from mast cells and basophils.
These cells, if sensitized by IgE antibodies attached to their surface membranes, degranulate explosively when exposed to the appropriate antigen.
This type of release also requires energy and calcium.
Degranulation leads to the simultaneous release of histamine, ATP, and other mediators stored in the granules.
Histamine released by this mechanism is a mediator in immediate (type I) allergic reactions, such as hay fever and acute urticaria.
Substances released during IgG or IgM-mediated immune reactions that activate the complement cascade also release histamine from mast cells and basophils. Examples: C3a, C5a.
Briefly discuss the role of histamine in modulating inflammatory and immune responses.
Upon injury to a tissue, released histamine causes local vasodilation and leakage of plasma-containing mediators of acute inflammation (complement, C-reactive protein), and antibodies.
Histamine has an active chemotactic attraction for inflammatory cells (neutrophils, eosinophils, basophils, monocytes, and lymphocytes).
Histamine inhibits the release of lysosome contents and several T and B-lymphocyte functions.
Inflammatory and immune functions of histamine are mediated by which receptors?
H2 and H4 receptors
Briefly discuss immunological release of histamine from mast cells and basophils.
✔ Certain amines, including drugs such as morphine and tubocurarine, can displace histamine from its bound form within cells.
✔ This type of release does not require energy and is not associated with mast cell injury or explosive degranulation.
✔ Chemical and mechanical mast cell injury causes degranulation and histamine release.
State the distribution of each of the four histamine receptors.
H1: smooth muscle, endothelium, brain
H2: gastric mucosa, cardiac muscle, mast cells, brain
H3: presynaptic autoreceptors and heteroreceptors: brain, myenteric plexus, other neurons
H4: eosinophils, neutrophils, mast cells, CD4 T cells
Briefly discuss the post-receptor mechanism associated with the H1 insulin receptor.
Activation of H1 receptors, which are present in endothelium, smooth muscle cells, and nerve endings, usually elicits an increase in phosphoinositol hydrolysis and an increase in inositol trisphosphate (IP3) and intracellular calcium.
What kind of receptors are histamine receptors?
G-protein coupled receptors
State three typical responses to histamine.
(1) pain and itching in the skin
(2) bronchoconstriction
(3) vasodilation of small blood vessels
Histamine H1 receptors mediate many pathological processes including ________.
allergic rhinitis, atopic dermatitis, conjunctivitis, urticaria, bronchoconstriction, asthma, anaphylaxis
Briefly discuss the “triple response” in relation to histamine.
This is a classical reaction observed when histamine is injected intradermally. It consists of three components:
(1) Red spot: Within seconds of the injection, a localized red spot appears at the injection site. This is due to the direct vasodilatory effect of histamine on the blood vessels, causing them to widen and increase blood flow.
(2) Flare: Surrounding the initial red spot, a larger red area or “flare” develops. This is caused by the reflex vasodilation of arterioles and capillaries in the surrounding area. The flare is mediated by an axon reflex, where the sensory nerves release additional histamine and other mediators.
(3) Wheal: After a few minutes, a raised, pale swelling or “wheal” forms at the injection site. This is due to the increased permeability of the blood vessels, allowing plasma to leak into the surrounding tissues and cause localized edema.
