--HISTAMINE—

 AUTOCOIDS = produced by wide variety of cells in body, have intense biological activity, but generally act locally (w
exception of ‘anaphylactic shock’) at site of synthesis and release.
 Known as local hormone but differ from hormones.
 Classical autocoids : histamine, 5-HT, PG, LC, PAF, plasma kinin, angiotensin
 Histamine : major mediator of inflammatory process ; it also has significant role in regulating gastric acid
secretion & in neurotransmission.
: present mostly within storage granules of mast cells
: tissues rich in histamine are skin, gastric & intes, mucosa, lung, liver & placenta
: non-mast cells histamine occur in brain, epidermis, gastric mucosa, & growing regions,
Blood, most body secretion, venoms, & pathological fluid

Synthesized fr a.a L-histidine------------------------------------->histamine

mainly in mast cell, basophil, enterochromaffin-like cell in gastric mucosa, certain neuron
SYNTHESIS that use histamine as neurotransmitter

SLOWLY TURNING OVER POOL

~~~located mainl y in mast cell & basophil, stored in large granules
~~~several weeks required to replenish histamine stores after degranulation
RAPIDLY TURNING OVER POOL
~~~is located in gastric ECL cell & histaminergic CNS neurons. these cell synthesize &
release histamine for gastric acid secretion & neurotransmission but they do not store
STORAGE histamine unlike mast cell & basophil
~~depends on physiologic stimuli, eg: in gut, histidine decarboxylase activated after eat

once histamine released, liver rapidly degrade it into inert metabolites : imidazole-acetic
RELEASE acid. which can be measured in urine and the level of it used to determine amount of
histamine released systematically.

 HISTAMINE RECEPTORS :
 H1 ~ involve in inflammation & allergic rxn
~ present on vascular endothelial cell & s.m cell
~ stimulation cause : 1. Edeme
2. Bronchoconstriction
3. sensitization of primary nerve terminal, depend on tisu type

~ also on pre-synaptic membrane of histaminergic neuron in hypothalamus,as autorecep to inhibit further hista.

 H2 ~ major fx to mediate gastric acid secretion in stomach

~ present on parietal cell in gastric mucosa
~ also in cardiac muscle cell, some immune cell, certain presynaptic neuronal membrane

 H3 ~ little know about its action, present on presynaptic nerve terminal in CNS, they limit histamine release
~ to limit histaminergic action in gastric mucosa & bronchial smooth
 1. STOMACH

 Histamine is a potent stimulator of acid secretion by parietal

cell in gastric mucosa
 One of 3 molecule that regulate acid secretion in stomach,
others are gastrin & ACh
 Primary role of histamine in gastric is to potentiate gastrin-
induced acid secretion

3. CNS

 As neurotransmitter
 Both histaminergic neuron
w histidine decarboxylase 4. HEART
& histamine recep are
present in hypothalamus w
ACTION OF HISTAMINE  Minor increase
diffuse projection thruout in force & rate
brain & spinal cord of contraction
 Not well understood,
believed involve in
maintenance of
wakefulness & appetite
supressant

2. SMOOTH MUSCLE- some s.m fibers contract while other relax

 Bronchial s.m – contracts

 Terminal arterioles & post-capillary venules – dilates
 Veins – constrict
 S.m in bowel, bladder, iris, uterus – constrict but effect not significant
 Vascular endothelium – contract; result in separation of these cell one
another—allow escape of plasma protein & fluid fr post-capillary venules &
causes edema
 Peripheral sensory nerve terminal- sensation of itch & pain result fr
depolarizing action of histamine on afferent nerve terminal. Responsible for
pain & itch ezperienced after insect bite or sting