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serotonin

Serotonin physiology

Serotonin (5-OH tryptamine):

  • It had been known that when blood clotted, a vasoconstrictor was released in serum & this was a nuisance in studies in late 1940's during searches for vasoconstrictors. In 1948, it was crystallised & named serotonin & soon found to be 5-HT.
  • Also, the substance that produces peculiar histochemical properties to enterochromaffin cells of GIT mucosa was discovered to be a GIT stimulating factor & was called enteramine in late 1930's, this was shown to be 5-HT in 1952.
  • 5-HT was discovered in brain & led to observations that LSD & other potent hallucinogens were structurally similar to 5-HT & inhib. smooth muscle responses to 5-HT in 1953, & reserpine found to lower [5-HT] in brain in 1957.
  • 5-HT, like histamine, is widely distributed in animal & plant kingdoms & also present in many venoms (eg. nettle, wasp, scorpion). In addition, there are natural congeners with varying degrees of periph. & central 5-HT activity:
    • DMT & bufotenine in cahobe bean (Carribean aborig. rites)
      • both can be formed in mammals from tryptamine & 5-HT;
      • various hallucinogenic mushrooms;

Physiology of serotonin:

  • 90% of 5-HT in adult body located in EC cells of GIT & most of remainder in platelets & CNS but not mast cells in humans;
  • 5-HT is synthesised from tryptophan in EC & CNS cells but platelets need to actively uptake 5-HT from plasma esp. during GIT passage;
  • The 5-HT is stored in secretory granules with turnover times in brain of 1hr & in EC cells of 17hrs;
  • The active uptake transport systems in platelets & in tryptaminergic neurons is similar to neuronal uptake of catecholamines & is influenced by many of the tricyclic antidepressant drugs;
  • 5-HT is oxidatively deaminated by MAO → 5-OH indoleacetaldehyde which is promptly degraded to 5-HIAA (excreted in urine) by aldehyde dehydrogenase or to 5-HTOL by alcohol dehydrogenase.
  • The 3 enzymes are present in liver & tissues that contain 5-HT.
  • Ingestion of ethanol diverts 5-HIacetaldehyde from oxid. path to reductive path due to incr. incr.NADH → incr. excretion 5-HTOL & decr. 5-HIAA;

EC cells:

  • basal secretion incr. by mechanical stim., hyperton., NA, vagal stim.;
  • secreted with other autacoids: substance P & motilin;
  • involved in neural network that regulates intestinal motility;

EC tumours

  • → markedly increased 5-HT & other autacoids
  • → carcinoid synd;
  • → may cause trytophan defic. → decr. niacin synth. → pellagra;

Platelets:

  • During aggreg. at sites of vasc. injury, platelets release 5-HT along with ADP, arach.acid metab. (eg thromboxane A2), & other mediators;
  • Platelet memb. 5-HT2 receptor stimulation → incr. aggreg. which is normally a weak response, but maximal plat.activ. if low [] of other agonists such as collagen → amplifies aggreg. & clot form.
  • If exposed vasc. smooth muscle cells then released 5-HT causes vasoconstriction aiding haemostasis;
  • 5-HT may also play a role in vasoconstriction assoc. with:
    • Raynaud's dis; atheroslerosis; certain essential HT;
    • spasm of newly formed collateral arteries;
serotonin.txt · Last modified: 2008/09/22 13:05 (external edit)