The Effects of 5‐hydroxytryptamine and Its Antagonists on Tidal Air

Abstract

Various reports suggest that 5-hydroxytryptamine (5HT) can cause bronchoconstriction. Thus, Reid and Rand (1952) (Gaddum, Hebb, Silver, and Swan, 1953) and guinea-pig (Bhattacharya, 1955). A constrictor effect of 5HT has also been noted in the tracheal chain of the guineapig (Freyburger et al., 1952) and cat (Sinha and West, 1953). Furthermore, 5HT administered as an aerosol causes dyspnoea in the guinea-pig, resembling that produced by histamine or acetylcholine (Herxheimer, 1953a(Herxheimer, , 1953b(Herxheimer, , and 1955.As yet, the effect of 5HT on tidal air has not been investigated in the intact and spinal animal. It therefore seemed of interest to make such an investigation with a view to obtaining further information on the mode of action. Another purpose of the study was to investigate whether agents found to be potent antagonists of 5HT in isolated organs in vitro also antagonize the bronchoconstriction induced by SHT in vivo. METHODSCats were anaesthetized with a mixture of chloralose (0.05 g./kg.) and urethane (0.5 g./kg.) administered subcutaneously. In the course of some experiments first the vagi were cut and later the spinal cord was sectioned at C 1. Guinea-pigs were anaesthetized by intraperitoneal administration of urethane (1.2 g. /kg.). Spinal cats and guinea-pigs were also used, the operation being conducted under ether anaesthesia.

On the bronchoconstrictor effect of serotonin. Bronchographic studies on rabbits and guinea‐pigs

“…The fact that it could be readily seen in etherized guinea-pigs, and only poorly or not at all in anaesthetized rabbits, conforms with the results of experiments with indirect methods by other authors (Schneider & Yonkman, 1954;Konzett, 1956). …”

“…Helsinki, Finland (Received 24 October 1960) Serotonin is known to be an effective bronchoconstrictor in animals (Herxheimer, 1953; Konzett, 1956;Balzer, Greef & Westermann, 1956). In man a clinical sign of this action is the fact that patients suffering from metastasizing carcinoid tumour often have asthmatic attacks; and Herxheimer (1955) found that although inhalation of serotonin aerosol in four normal cases had no effect, in three out of six asthmatics it elicited severe asthmatic attacks which were abolished by iso-propyladrenaline.…”

The Pharmacology of Chymotrypsin Administered by Inhalation

“…Subsequently (Eichler and Sebening, 1959) Konzett (1956) have emphasized the difficulty of attributing a decrease in tidal air to bronchoconstriction rather than pulmonary congestion. With histamine or 5-hydroxytryptamine the response is immediate and certainly points to a direct action on the bronchial musculature (Konzett, 1956). The tidal air change elicited by trypsin is of the same type, whereas chymotrypsin, in high doses, produces its effect gradually, reaching a plateau only after several minutes.…”

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

“…Bronchospasm due to 5-HT has been reported previously in the isolated guinea-pig trachea (Sinha & West, 1953;Balzer, Greeff & Westermann, 1956) as well as in the intact cat (Reid & Rand, 1952;Comroe, Lingen, Stroud & Roncoroni, 1953;Konzett, 1956) and dog (Rahamimoff & Bruderman, 1965). The predominant effect of 5-HT in most animal species is therefore bronchoconstriction.…”