histamine
Table of Contents
histamine physiology, receptors and antihistamines
see also:
introduction
- 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:
- eg. cimetidine, ranitidine, etc
H3 receptors:
- ? inhib. coupling to adenylyl cyclase;
- H3 antagonists:
- thioperamide -but potential use not established.
histamine.txt · Last modified: 2012/05/01 07:08 by 127.0.0.1