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histamine physiology, receptors and antihistamines


  • 1st detected (with ACh) in ergot extracts as stimulants of uterus, but later both proved to be contaminants of ergot due to bacteria;
  • 1st isolated from body 1927 in various tissues hence histamine;
  • Almost all mammalian tissues contain it - mainly stored in mast cells where it is synthesised from histidine via L-histidine decarboxylase & then store it in secretory granules along with heparin, ECF-A, NCF-A & certain enzymes which is exocytosed if i/cell. [Ca] is increased;
  • Turnover rate of histamine in granules is slow & when tissue depletion occurs, may take weeks for normal levels to return;
  • Histamine is rapidly made & continuously released in non-mast cell sites:
    • epidermal cells; gastric mucosa cells; CNS; rapid turnover cells;
  • Histamine is metabolised to inactive metabolites (urine excreted) by:
    • histamine-N-methyltransferase ⇒ N-methylhistamine which is converted by MAO to N-methyl imidazole acetic acid;
    • nonspecific diamine oxidase (DAO) ⇒ imidazole acetic acid

physiologic roles:

  • mast cell response in immunity:
    • H1:
      • bronchoconstriction, rapid vasodilation, increased capillary permeability, contraction GIT;
      • stimulate afferent vagal N endings ⇒ reflex bronchospasm;
      • NB. in man most bronchospasm via other mediators;
    • H2:
      • slow, sustained vasodilation; (? increased capill.perm.); bronchodilation
    • triple response of Lewis (1927):
      • local red spot few sec⇒1min due to local histamine;
      • brighter flare 1cm slowly due to his-ind. axon reflex;
      • wheal in 1-2 min. due to oedema;
  • CNS neurotransmitter:
    • H1: reg. of drinking, T, ADH, BP, pain perception;
    • H3: presyn.reg. synth./release of his. in his.N terminals
  • Gastric histamine secretion ⇒ main factor in incr. parietal acid secret.(H2);
  • Epidermal release ⇒ pain/itch via stim. of nerve endings (H1);

Histamine Receptors & antagonists:

H1 receptor:

  • coupled to phospholipase C
    • ⇒ synth. of IP3 & diacylglycerols from Plipids in cell membrane;
      • IP3 ⇒ rapid Ca release from ER;
      • DAG & Ca activate:
        • Ca/calmod.-depend. protein kinases
          • ⇒ eg. myosin light chain kinase ⇒ contraction;
        • Plipase A2: (eg. on vasc. endothelial cells)
          • ⇒ eg. local prod. EDRF incr. ⇒ vasodilatation;
          • ⇒ eg. incr. PGI2 ⇒ vasodilatation;
  • H1 antagonists:

H2 receptors:

  • coupled to adenylyl cyclase ⇒ c-AMP incr. (ie. similar to beta-adren)
    • ⇒ activ. of c-AMP depend. protein kinases:
    • ⇒ decr. gastric acid secretion from most stimuli;
  • H2 antagonists:

H3 receptors:

  • ? inhib. coupling to adenylyl cyclase;
  • H3 antagonists:
    • thioperamide -but potential use not established.
histamine.txt · Last modified: 2012/05/01 17:08 (external edit)