Serotonin (5HT) Receptor subtypes. Sites of 5HT action. Stored and secreted by -- Enterochromaffin-like (ECL) cell of GI mucosa --Platelets □ ECL cells synthesize 5HT from tryptophan and store 5HT and other autacoids (substance P, kinins )
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Stored and secreted by
--Enterochromaffin-like (ECL) cell of GI mucosa
□ ECL cells synthesize 5HT from tryptophan and store 5HT and other autacoids (substance P, kinins)
□ Platelets don’t synthesize 5HT but take up from circulation by active transport to store in secretory granules
ECL Cells: Basal release of 5HT augmented by mechanical stretching (like caused by intake of food or hypertonic saline).Also has GI motility stimulation effect.
Clinical implication: Synthesis in large amount by carcinoid tumors result in tryptophan deficiency (pellagra)
Platelets: Platelets when make contact with injured endothelium, release substances (thrombin, thromboxane A2) that promote platelet adhesion and release of 5HT. Then 5HT on binding to 5-HT2A receptors elicit weak aggregation response [markedly enhanced in presence of collagen].
5HT also exerts a direct constrictor effect, promoting hemostatis [locally released kinins, thromboxane A2 enhance this action]
CVS system: Classical response is vasoconstriction [in renal, pulmonary and cerebral vasculatures]
Has positive inotropic and chronotropic effect on heart
Clinical implication: sometimes may cause extreme bradycardia (slow heart rate) and hypotension
In esophagus, 5HT acting on 5HT4 receptors causes either relaxation or contraction , depending on species
5HT3 receptor activation on vagal and other afferent neurons causes emesis
Clinical implication: 5HT3 antagonists [Ondansetron] used as anti-emetic
Local Effect: Release of enteric 5HT in response to Ach increases intra-luminal pressure and trigger peristaltic contraction
CNS: sleep, cognition, motor activity, sensory perception, nociception and temperature regulation are influenced by 5HT
Clinical implication: 5HT antagonists are typical antipsychotics