2.8 - Histamine

Histamine

- an autocoid (“self-remedy”)

- mediator of anaphylaxis and inflammation, and gastric acid secretion

Histamine synthesis

decarboxylation of histidine catalyzed by L-histidine decarboxylase

histamine storage/distribution

- rich at sites of potential injury (bound in mast cells and basophils)

- cells of stomach release histamine to ↑ stomach acid from parietal cells

- found in brain 

Histamine metabolism

- 2 pathways: Histamine-N-methyltransferase → MAO (terminates signaling at synaptic cleft) or Diamine oxidase → phosphoribosyl transferase

histamine receptors

- 4 metabotropic 7 TM GPC receptors

- both excitatory and inhibitory, depending on signal transduction

H1 (Histamine receptor)

- excitatory Gq found in smooth muscle, PNS SN, and CNS

- increased cotrical activity, arousal, and wakefulness

H2 (Histamine receptor)

- Gs located on smooth muscle and pariental cells

- activation causes release of stomach acid

H3 (Histamine receptor)

inhibitory Gi/o autoreceptor found in the CNS cortex and subcortex

H4 (Histamine receptor)

- Gi receptor located peripherally on immune cells

- strong promotor of pruritus (itching sensation) and burning feelings

functions of Histamine

inflammatory response, sexual f(x)/libido, gastric acid secretion

inflammatory response

- Mast cell + basophil granules release histamine ↑swelling, vasodilation, other autacoids → Causes hypersensitivity to pain

- ↑ bronchoconstriction; mediates allergy responses.

sexual f(x) and libido

- H2R antagonists produce ED

- direct histamine injection reverses

gastric acid secretion

Enterochromaffin-like (ECL) cells in the stomach release histamine → stimulating H2 receptors → release of stomach acid 

pH

Histamine release decreases with _____.

Tuberomammillary pathway

- H1 receptors + histamine as NT

- Histamine from the hypothalamus affects brain areas linked to arousal, cognition, and neuroendocrine functions.

- Cognition and Sedation: H₁ agonists boost cognition; antihistamines cause sedation and regulate pain sensitivity.

- Pain and Body Regulation: Histamine impacts pain sensitivity, appetite, body temperature, and cardiovascular activity.

neuromodulation of Histamine

- Presynaptic H3 receptors in brain act as autoreceptors: reducing their own release

- decrease release of ACh, NE, DA and serotonin to modulate nociception + signal satiety