PCOL HISTAMINE

AUTACOIDS (Local Hormones)

Definition

Autacoids are:

Also known as “local hormones”

Endogenous substances with biological activity

Not stored or released from endocrine glands

Not circulated in the bloodstream

Synthesized at the site of action

Produce localized and short-lasting effects

👉 They act near the site where they are formed and regulate inflammation, smooth muscle activity, vascular tone, and neurotransmission.

General Characteristics of Autacoids

Rapid synthesis and degradation

Act via specific receptors

Important in pathophysiology and drug therapy

Many drugs either block or mimic autacoid actions

CLASSIFICATION OF AUTACOIDS

1. Biologically Active Amines (Biogenic Amines)

Derived from amino acids

Rapid onset of action

Mainly involved in allergic reactions and neurotransmission

Examples:

Histamine → from histidine

Serotonin (5-HT) → from tryptophan

2. Lipid-Derived Autacoids (Eicosanoids)

Derived from 20-carbon unsaturated fatty acids

Synthesized from arachidonic acid

Act locally and rapidly degraded

Examples:

Prostaglandins

Leukotrienes

Thromboxanes

👉 Important in inflammation, pain, fever, platelet aggregation, and bronchial tone

3. Vasoactive Polypeptides

Short peptide chains

Cause vasodilation or vasoconstriction

Affect blood pressure and smooth muscle

Examples:

Kinins (e.g., Bradykinin)

Angiotensin

Vasopressin

Substance P

4. Endothelium-Derived Autacoids

Produced by vascular endothelial cells

Regulate vascular tone and blood flow

Examples:

Nitric Oxide (NO) → vasodilation

Endothelin → vasoconstriction

Natriuretic Peptide

5. Ergot Alkaloids

Derived from Claviceps purpurea (fungus)

Act on serotonin, dopamine, and adrenergic receptors

Used in migraine and postpartum hemorrhage

SUMMARY TABLE: CLASSES OF AUTACOIDS

Class

Origin

Biologically active amines

Amino acids

Lipid-derived (Eicosanoids)

Arachidonic acid

Vasoactive polypeptides

Peptides

Endothelium-derived

Endothelial cells

Ergot alkaloids

Fungal origin

HISTAMINE

Definition

Histamine is a biogenic amine formed by decarboxylation of the amino acid histidine.

Biosynthesis of Histamine

Precursor: L-Histidine

Enzyme: L-histidine decarboxylase

Cofactor: Pyridoxal phosphate (Vitamin B₆)

Reaction:

L-Histidine → Histamine

Sites of Histamine Biosynthesis

Mast cells (highest amount)

Basophils

Stomach

Enterochromaffin-like (ECL) cells

Central Nervous System (CNS)

Storage of Histamine

Stored mainly in mast cells and basophils

Present in granules

Bound as a complex with:

Heparin

ATP

Acidic protein

👉 This storage prevents spontaneous release.

Distribution of Mast Cells

Mast cells are abundant in:

Respiratory tract

Skin (especially hands and feet)

Gastrointestinal tract

Blood vessels

Importance of Histamine (High-Yield Points)

Major mediator of allergic reactions

Involved in:

Vasodilation

Increased vascular permeability

Gastric acid secretion

Neurotransmission

TYPES OF HISTAMINE RELEASE

Histamine can be released from mast cells and basophils by two main mechanisms:

1. Energy- and Ca²⁺-Dependent Degranulation

(Immunologic Release)