Histamine and Its Receptors Quiz

Histamine

• Histamine is a biological amine with a hydrophilic structure.
• It's composed of an imidazole ring and an amino acid connected by two methylene groups.
• Found in non-neural tissue, including plant and animal tissues, some venoms, and stinging secretions.
• Most tissue histamine is contained within granules (vesicles) inside mast cells and basophils.
• Stimuli trigger the release of histamine from mast cells, enabling it to act on surrounding tissues.

Histamine Receptors

• Four subtypes: H1, H2, H3, and H4.
• All are coupled with G proteins (GPCR).
• Different receptor subtypes are coupled to different G protein subtypes, resulting in varying intracellular signaling pathways.
• H1 receptors are found in endothelium, smooth muscle cells, and nerve endings, increasing phosphoinositol hydrolysis and intracellular calcium levels (Ca²⁺).
• H2 receptors are present in gastric mucosa, cardiac muscle cells, some immune cells, and increase intracellular cyclic adenosine monophosphate (cAMP) through Gs signaling.
• H3 receptors are mainly presynaptic, reducing neurotransmitter release by decreasing calcium influx through N-type calcium channels.
• H4 receptors are primarily found on leukocytes, modulating the production of these cells and potentially mediating histamine's effects on cytokine production.

Histamine's Physiological Functions

• Mediator of immediate allergic and inflammatory reactions.
• Significant role in gastric acid secretion.
• Functions as a neurotransmitter and neuromodulator.
• Plays a role in chemotaxis of white blood cells (WBC).
• No clinical application as a therapeutic agent.

Release of Histamine

• Release occurs through chemical and mechanical methods.
• Certain drugs, like morphine and tubocurarine, displace histamine from its complex with heparin and proteins.
• Loss of granules from mast cells also releases histamine.
• Chemical and mechanical injury to mast cells leads to degranulation and histamine release.
• Non-mast cell histamine is also found in various tissues, including the brain.
• Endogenous neurotransmitter histamine plays a role in brain functions, including neuro-endocrine control, cardiovascular regulation, thermal and body weight regulation, and arousal.

Antihistamines

• Two main generations: First and second generation.
• First generation:
  • Examples: promethazine, ciproheptadine.
  • Often have anticholinergic effects and can cause sedation.
• Second generation:
  • Examples: fexofenadine, loratidine, cetirizine.
  • Less likely to cause sedation.
  • Minimal anticholinergic effects.

Pharmacology of Antihistamines

• Act through a reversible competitive antagonism at the H1 receptor.
• Clinically used to prevent and treat allergic reactions, such as allergic rhinitis and urticaria.
• H1 antagonists are also effective in preventing motion sickness when combined with ephedrine or amphetamine.

Adverse Effects of Antihistamines

• Common: sedation and antimuscarinic actions.
• Less common but serious: excitation and convulsions in children, postural hypotension, and allergic responses.

H2-receptor Antagonists

• Significant in treating peptic ulcer disease and related GI complaints.
• Decrease gastric acid secretion.
• Have low toxicity and are widely used in the US.
• Available over-the-counter (OTC).

H3 and H4 Ligands

• No selective H3 or H4 ligands currently available for clinical use.
• Selective H3 ligands have potential for treating sleep disorders, obesity, cognitive and psychiatric disorders.
• H4 blockers may prove useful in treating chronic inflammatory conditions, such as asthma.

Test your knowledge on histamine, its structure, and functions. This quiz covers the four subtypes of histamine receptors and their roles in various physiological processes. Evaluate your understanding of how histamine interacts with different tissues and the implications for health and disease.