Pharmacological significance of biogenic amines in the lungs: 5‐hydroxytryptamine

1 Passive lung anaphylaxis (PLA) was investigated in rats sensitized by the intravenous injection of high titre reaginic antiserum prepared in rats. 2 The effect of various pharmacological antagonists on anaphylactic bronchoconstriction in vivo were examined. An antihistamine (mepyramine), a kallikrein inactivator (aprotinin) or a prostaglandin synthesis inhibitor (aspirin) did not inhibit PLA, whereas an anti-5-hydroxytryptamine agent (methysergide) and an anti-slow reacting substance-A agent (FPL, 55712) significantly reduced the response. 3 Isolated perfused lungs taken from sensitized rats released, on challenge with the sensitizing antigen, histamine, 5-hydroxytryptamine, slow reacting substance of anaphylaxis (SRS-A) and prostaglandins, but no rabbit aorta contracting substance (RCS). 4 Disodium cromoglycate inhibited both anaphylactic bronchoconstriction in vivo and the anaphylactic release of mediators in vitro. Inhibition in vivo was dose-related. 5 Mediators from the intestine, the primary shock organ of anaphylaxis in the rat, did not contribute to the lung response. 6 Vagal reflex pathways were found not to be important in PLA in vivo. 7 The relationship between the mediators released following antigen challenge of passively sensitized rat lung in vitro and passive lung anaphylaxis in vivo is discussed.

Section: Discussionmentioning

confidence: 54%

Mediators of Passive Lung Anaphylaxis in the Rat

Farmer¹,

Richards²,

Sheard³

et al. 1975

“…The administration of reserpine, 5-HT or 5-hydroxytryptophan, which influences the 5-HT content of the lungs, does not influence histamine content (Sadavongvivad, 1970;Aviado & Sadavongvivad, 1970). Only two conditions were found to affect the concentration of histamine in the lung.…”

Section: Discussionmentioning

confidence: 87%

“…One group served as control; a second group was sensitized 24 hr previously by an intracardiac injection of rabbit serum containing antibodies against bovine serum albumin. On the day of the experiment, 1 ml of saline was injected intracardially under ether anaesthesia and the lungs were removed for analysis of biogenic amines (see method reported by Sadavongvivad, 1970). A third group was also sensitized 24 hr previously, and the antigen was administered 4 min before killing the animal.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Pharmacological significance of biogenic amines in the lungs: histamine

Aviado

Sadavongvivad

1970

Self Cite

Summary . Eight animal species were investigated for the histamine content of the lung and can be divided into two groups: the low‐level group, ranging from 2 to 7 μg/g, consisting of the mouse, rat, guinea‐pig and rabbit; and the high‐level group, ranging from 12 to 35 μg/g, consisting of the cat, dog, goat and human. In two species of the high‐level group (cat and dog) the amount of histamine that elicited an increase in pulmonary resistance was one‐fifth to one‐tenth of the dose that elicited an increase in species of the low‐level group (rat and rabbit). There is an inverse relationship between the content of histamine and the dose of histamine that produces a 25% increase in pulmonary resistance. . Anaphylaxis increases the histamine content of the lung of the rabbit but not of the lung of the guinea‐pig. In both species, anaphylaxis is accompanied by an elevation of the concentration of 5‐hydroxytryptamine in the lung, indicating the trapping of platelets in the lung. . The development of severe parasitaemia in the mouse inoculated with Plasmodium berghei is accompanied by an elevation of the histamine content of the lung. This increase appears to be part of the response of the lung to parasitaemia.

“…Interestingly, goat lung contains large quantities of 5-HT (Sadavongvivad, 1970). Tryptamine analogues have been considered as aetiological factors in the induction of pulmonary oedema and emphysema in goats and cattle (Carlson, Dyer & Johnson, 1968;Carlson, Yokoyama & Dickinson, 1972).…”

Section: Discussionmentioning

confidence: 99%

5‐hydroxytryptamine Induces Relaxation of Goat Pulmonary Veins: Evidence for the Noninvolvement of M and D‐tryptamine Receptors

Chand

1981

1 Reactivity of goat isolated pulmonary arteries and veins to a variety of vasoactive agents was investigated. 2 Bradykinin (Bk), acetylcholine (ACh), noradrenaline (NA), prostaglandin Al (PGA1), PGE2, PGF21 and histamine induced dose-dependent contractile responses on veins; 5-hydroxytryptamine (5-HT) induced veno-relaxation. Angiotensin was virtually inactive. 3 Angiotensin, NA, Bk, histamine and 5-HT produced concentration-dependent contractile responses on the arterial strips; these arteries failed to respond to ACh, PGA1, PGE2 or PGF2,. 4 The pulmonary veno-relaxant response to 5-HT was found to be resistant to propranolol, indomethacin, metiamide, cimetidine, methysergide, atropine and morphine. These findings appear to exclude the involvement of adrenergic mechanisms and prostaglandin generation as well as activation of classical M and D-tryptamine receptors by 5-HT in the goat pulmonary veins. This response may be mediated via a presynaptic inhibitory 5-HT receptor. 5 5-HT-induced arterial contractile responses were antagonized by methysergide, showing the occurrence of classical D receptors in the goat pulmonary artery. 6 It is concluded that differential reactivity of pulmonary arteries and veins to vasoactive agents may play differential role(s) in the pathophysiology inflammatory activity in goat pulmonary veins.Recently, there has been some interest in the autonomic and autacoid pulmonary pharmacology of farm animals (Eyre, 1971; 1975,a,b;Hanna & Eyre, 1978; Chand, DeRoth & Eyre, 1979;Chand & Altura, 1980). During the course of one of these investigations, 5-hydroxytryptamine (5-HT) was found to relax goat trachea (Chand et al., 1979). A preliminary study, in our laboratory, indicated that goat pulmonary veins were also relaxed by 5-HT. The pharmacological characterization of this unusual relaxant response to 5-HT on goat pulmonary veins was therefore undertaken. MethodsSeven adult goats of either sex, weighing 50 to 150 lbs, were killed by shooting and exsanguination. The lungs and heart were immediately dissected out and placed in ice-cold oxygenated Krebs-Henseleit solution. The remainder of the experimental procedures of pulmonary disease. 5-HT may exert an antiwere identical to those described earlier (Eyre, 1975,a,b; Chand et al., 1979). In brief, pulmonary veins and arteries were isolated, dissected out and cut into spiral strips. Each strip was longitudinally dissected into twin 'identical strips'. From each animal, 3 to 6 pairs of pulmonary vein strips were used within 12 to 24 h. Tissues were mounted in pairs in 15 ml isolated organ baths, containing Krebs-Henseleit solution, mixed with 95% 02 and 5% Co2 at 37'C. The composition of the Krebs-Henseleit solution was (mmol/l): NaCl 118, KCI 4.70, CaCI2 .2H20 2.5, KH2PO4 1.2, MgSO4.7H20 1.2, NaHCO3 25.0 and glucose 10.0. The strips were allowed to equilibrate for 2 h under a resting load of 2 g. Single or cumulative dose-response curves to one or two agonists were recorded with a Narco Isotonic Myograph Transducer connected to a Fisher Recor...