biosynthesis and source Histamine is amine of the amino acid histidine Histamine is synthesized by enzymatic decarboxylation of histidine

this book Many illustrious personalities (physiologist /pharmacologists/ clinicians) have worked on histamine some prominent names being Dale. Laidlaw, Best and Lewis. Chemistry, biosynthesis and source Histamine is amine of the amino acid histidine Histamine is synthesized by enzymatic decarboxylation of histidine. the enzyme beinq histidine decarboxylase In our body histamine can be obtained from many tissues but most notably from the mast cells of the tissues and the blood basophilc. Other important sources are gastro intestinal mucosa and CNS. In the mast cells, histamine is completed with heparin and the heparin histamine complex is dissociated to cause, release of pharmacologically active histamine In allergic states following the contact of the antigen with a mast cell, the mast Cell is diegranulated (= mast cell granules are lysed) Dhistarnme is released from the mast celt Certain bee venom and stings ol certain insects are rich in histamme Actions The actions of hrstamine cart be divided into two major categones. (A) On smooth muscles, and (B) On exocnine glands of stomach Besides hislamine has (C) some other (miscellaneous) action. Actions on smooth muicles 1 It causes relaxation of Ihe anenoles and probably also of [he smooth muscles of precapillary sphincter, leading la engorgement of the capillaries This action used to be designated as "capillary dilatation* by our forofathers, but now it is known that true capillaries are devoid of muscles and hence active dilatation is not possible in them. 2. Hislamine causes contraction of bronchial (specially in susceptible persons) and intesimal smooth muscles leading to bronchospasm and diarrhea. Recall, mast cells occur plentifully in mucous membrane tracheobronchial tree. An injection of histarmne therefore can produce a shafp fall of blood pressure and violent attack of asthma, theie may also be uflicaria Fall of BP is due to acute dilaiation of the artenoles (Ihe 'resistance vessils) Urticaria (as well as Inple response', see chap 10, sec V, cutaneous circulation), is due to transudatB of fluid from the capillary to the tissue which in turn is due to capillary engorgement Ultimately, speaking, histamine injection in susceptible persons can produce, anaphylactic shock, characterized by severe fall of BP and asthma Action on secretion of eiocnne glands The tote of nisiamirie in gasinc acid secretion has been discussed in chap 3. sec III. In short, histamme stimulates the parietal calls of the stomach and thus increases the secretion of MCI Miscellaneous action 1 In addition, histamme also is related to the pain and itching sensation. 2. Some rapidly growing tissues produce hrstamine in large amounts Thus, embryos, regenerating liver and rapidly healing wounds produce histamme It is possible. 1. hat for (he smooth functioning of the raprdty growing (issues, histamme is necessary 3 Some neurons of the brain are hisiammergic. ie. 1har neurotransmitters is histamine Such histaminergic neurons play a role m therrnoregulalion by hypolhalamus Drugs and histamine Many drugs, especially in susceptible individuals liberate histamine Such drugs, when consumed by these individuals, produce vanous allergic manifestations on shin, like urticaria, itching and triple response after ilchmg Such drugs, presumably on coming in contact with mast cells cause membrane perturbation n degranulation Histamme receptors There are at least two sub lypes of hotamine receptors on the cellular membrane H1 and 22 receptors 1 Contraction or relaxation of the smooth muscles ate due to combination of hisiamme and HI receptor Therefore, drugs which are HI receptor therefore, drugs which ire h1 anlagonists, oppose tftese actions (e g urticaria, triple response following itching elc ) of histamme Such drugs are called classical anlmisiammics and include diphenhydremine (benadryl). iripelennamine (pynbenzamme), promelhazine (phenergan), and chlorpheniramine 2. Oxyntic cells of the stomach contain H2 receptors and when H2 blockers are used, gasinc HCI secretion is mhibrled (for details see chap 3, sec III) Cimetidine and ranitidme are very popular H2 antagonists and are used evtensively in the treatment of paptic ulcer rt is possrbta that There are more than Two Types erf receptors for histamine, further. apart rlomlhi giitnc glands, H2 receplon are present in other sites also, however their functions are not clear) EICOSANOIDS AND PAF Introduction Burr and Bun m the 1920s discovered the essential fatly acids (Iinoletic. linolenic and the arachidonic acids, all of them are long chain fatly acids having more than one double bonds. Hence they are known by the generic name 'polyunsaturaled fatly acids). In the 1930s Kurzok and Uele of USA discovered that semen contains a subitance that tan cause contraction of uterus Sometime after the great US von Euler studied Ihe chemistry and some of the functions of this compound and named it 'prustaglandin', because the source of this matenalwas supposed to be the prostate (gland) Researches on prostaglandin became almost explosive since the 1960s and a large number of new compounds, (occurring naturally), were discovered As a result, as the things stand, todays position is as follows. The parent material in our body (= human body) is usually arachidonic acid (a C 20, polyunsaturated, ie, eicosanoic, acid) There are two great classes of compounds which can be synthesized in our body from the