Autacoids (Local Hormones) ~Histamine

 Autacoids (Local Hormones)

 Autacoids (Local Hormones) Definition:-

ü  The word "autacoids' come from the Greek "Autos" (self) and "Acos" (remedy), so autacoids basically can be defined as "the chemical substances produced within the body to help in the remedy of local injuries".

ü  Autacoids can be defined as [Active Substance in the Body'].

ü  Autacoids can have many different biological actions including modulation of the activity of smooth muscles, glands, nerves, platelets and other tissues.

ü  Local hormones: These hormones are secreted into the interstitial fluid and they act locally in two ways.                 

1)      Paracrine Hormones: Act on the neighboring cells

                  2)   Autocrine Hormones act on the cells from which they were secreted.

ü  Local hormones: Not released or stored in glands, not circulated in blood, are formed at the site of action & produce localized action.

ü  N.B: Endocrine hormones à see endocrine chapter.

 

 

 

Autacoids Classification:-

 

1-      Decarboxylated amino acids: 

    Histamine

    Serotonin

2-      Polypeptides:

     Angiotensin 

     Plasmakinin

     Vasopressin

     Atrial Natriuretic Peptide (ANP) 

     Vasoactive Intestinal Polypeptide (VIP)

     Substance P

3-      Eicosanoids: 

     Prostaglandins

     Leukotrienes.

 

 

Decarboxylated Amino Acids:-

Histamine

Histamine
Bio Synthesis	. - Histamine is formed by decarboxylation of the amino acid L-histidine,  a reaction catalyzed by histidine decarboxylase enzyme.
Storage	- Once formed, histamine is either stored or rapidly inactivation. Histamine is found in:        • Tissues: - It is found in most tissues but is present in high conc. in the lungs, skin      and fundus of the stomach (Enterochromaffin- Like; ECL cells).        • Cells:  - It is found largely in mast cells and basophils.        • Neurons:   Histaminergic neurons in the brain.
Release	A) Immunologic Release: - Hypersensitivity reaction (Type I) (immediate hypersensitivity): - Antigen (allergen) react with antibody (IgE) on the mast cell these reaction increase release of histamine from mast cells. B) Chemical and Mechanical Release: - Morphine and Tubocurarine, can displace histamine from its bound form within cells. This type of release is not associated with mast cell injury or degranulation.

 

 

Histamine Receptor Subtypes
Histamine exerts its biological actions by combining with specific cellular receptors located on the surface membrane.
Subtype	G-protein	Main Location	Main Function
H1	Gq	-Smooth muscle -Endothelium -Brain	- Spasmogenic effect smooth   muscle. - Vasodilatation. - Skin itching.
H2	Gs	- Mast cells  - Cardiac muscle - Gastric Mucosa - Brain	- Increase Gastric HCl secretion. - Cardiac stimulation.
H3	Gi	- Presynaptic autoreceptors	- Decrease neurotransmitter release.
H4	Gi	- Neutrophils - Eosinophils	- Plays a role in chemotaxis.

 

Histamine exerts powerful effects on smooth and cardiac muscle, on certain endothelial and nerve cells, on the secretory cells of the stomach, and on inflammatory cells.
Pharmacological Action	Nerves cells	- Histamine is powerful stimulant of sensory nerve endings, especially those mediating pain and itching. This effect mediated by Hı receptor and it is an important component of the urticarial response to insects.
	CVS	- Direct vasodilatation (H1) à rapid ↑ NO production:      Decrease in systolic and diastolic blood pressure.        Flushing, sense of warmth and headache.      Increase capillary permeabilityà Edema        formation.   - Increase heart rate: (Due to) 1) Direct stimulatory action on the heart (H2). 2) Reflex tachycardia (VD).
	Lung	Bronchoconstriction (H1):  - This effect cause death in histamine toxicity.  - Patients with asthma are very sensitive to    histamine. - Small dose of inhaled histamine have been used in   diagnosis of bronchial hyperreactivity in patients   with suspected asthma or cystic fibrosis.
	GIT	- Intestinal smooth muscle contraction (H1). - Histamine generally has insignificant effects on the   smooth muscle of the eye and genitourinary tract.
	Stomach	- Powerful stimulant of gastric acid secretion (H2).
	Nose	1) Runny nose and watery eyes (due to hyper-secretion from glandular tissue). 2) Sneezing (due to histamine-associated sensory neural stimulation). 3) Nasal congestion (due to vascular congestion associated with vasodilation   and increased capillary permeability).
	brain	- Histamine neurons in the brain increase   wakefulness and prevent sleep, block H1 receptor   in the brain cause sedation. - Hypothalamus H1 receptors in the brain are crucial   for the regulation of the diurnal rhythm of food   intake and the regulation of obesity.

  

Triple Response of Lewis"

- Intradermal histamine injection cause:

1) Red spot (extending few millimetres around the site of injection):

   - Caused by direct dilatation of small vessels.

2) Flare (extend about 1cm):

   - Caused by axon reflex.

3) Edema (Wheal) formulation:

   - Caused by increase capillary permeability.

 

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