Pathophysiological Roles of 5HT

PATHOPHYSIOLOGICAL ROLES

1. Neurotransmitter  5HT is a confirmed neurotransmitter in the brain; brain 5HT has a fast turnover rate. Cells containing 5HT are present in the raphe nuclei of brainstem, substantia nigra and few other sites—send axons rostrally (to limbic system, cortex and neostriatum) as well as caudally to spinal cord. 5HT is probably involved in sleep, temperature regulation, thought, cognitive function, behaviour and mood (imbalance may result in affective disorders and schizophrenia), vomiting and pain perception. Some serotonergic fibres are present in intestines also.

2. Precursor Of Melatonin in pineal gland. It is believed to regulate biological clock and maintain circadian rhythm.

3. Neuroendocrine Function The hypothalamic neurones that control release of anterior pituitary hormones are probably regulated by serotonergic mechanism.

4. Nausea And Vomiting Especially that evoked by cytotoxic drugs or radiotherapy is mediated by release of 5HT and its action on 5HT₃ receptors in the gut, area postrema and nucleus tractus solitarious.

5. Migraine 5HT is said to initiate the vasoconstrictor phase of migraine and to participate in neurogenic inflammation of the affected blood vessels. Methysergide (5HT antagonist) is an effective prophylactic and sumatriptan (5HT_1B/1D agonist) can control an attack. However, the role of 5HT in this condition is not precisely known.

6. Haemostasis Platelets release 5HT during aggregation at the site of injury to blood vessel. Acting in concert with collagen and other mediators, this 5HT accelerates platelet aggregation and clot formation. Thus, it serves to amplify the response. Its contractile action appears to promote retraction of the injured vessel. Both the above actions contribute to haemostasis.

7. Raynaud’s Phenomenon Release of 5HT from platelets may trigger acute vasospastic episodes of larger arteries. Ketanserin has prophylactic value in Raynaud’s.

8. Variant Angina Along with thromboxane A₂, 5HT released from platelets has been implicated in causing coronary spasm and variant angina. However, the inefficacy of anti 5HT drugs in this condition points to involvement of other mediators.

9. Hypertension Increased responsiveness to 5HT as well as its reduced uptake and clearance by platelets has been demonstrated in hypertensive patients. Ketanserin has antihypertensive property. 5HT has been held responsible for preeclamptic rise in BP.

10. Intestinal Motility Enterochromaffin cells and 5HT containing neurones may regulate peristalsis and local reflexes in the gut. This system appears to be activated by intestinal distension and vagal efferent activity.

11. Carcinoid syndrome The carcinoid tumours produce massive quantities of 5HT. Bowel hyper motility and bronchoconstriction in carcinoid is due to 5HT but flushing and hypotension are probably due to other mediators. Pellagra may occur due to diversion of tryptophan for synthesizing 5HT.