The Action of 5‐hydroxytryptamine and Some of Its Antagonists on the Umbilical Vessels of the Human Placenta

Abstract

The vasoconstrictor action of 5-hydroxytryptamine (5-HT) in the human placental preparation is about 10 times stronger than that of adrenaline and is antagonized by anti-adrenaline compounds like phentolamine. Both 5-HT and adrenaline are antagonized by yohimbine and chlorpromazine. Specific and strong anti-5-HT action is demonstrated for lysergic acid diethylamide (LSD) and tryptamine. Both LSD and tryptamine in larger doses have a vasoconstrictor action. Mescaline has no certain modifying effect on the action of 5-HT, but itself causes vasoconstriction in large doses. The antihistamine drug phenbenzamine in histamine blocking doses abolishes the action of 5-HT in half the preparations tested. The ganglionic blocking agent trimetaphan in large doses antagonizes the action of 5-HT added subsequently, and also, to a lesser degree, the effect of adrenaline. Hexamethonium and tetraethylammonium bromides are ineffective in this preparation. No certain modifying action of reserpine on subsequently added 5-HT could be demonstrated, and the same was true for heparin even in very high concentrations.5-Hydroxytryptamine (5-HT) continues to attract considerable attention as a possible factor in different experimentally produced psychotic conditions in animals and as a compound possessing vascular effects. Although 5-HT has rather weak and inconsistent effects upon the systemic blood pressure in different animals and in man (Erspamer, 1954), evidence is accumulating for its strong vasoconstrictor action in certain local vascular beds.In a previous report from this laboratory (Eliasson and Astrom, 1955), the pharmacological actions of a series of compounds were studied on the blood vessels of isolated human placentas. 5-HT was included in this series, and its actions were compared with those of adrenaline and noradrenaline. It was shown that 5-HT, in the same manner as the catechol derivatives, caused a constriction of the umbilical vessels and its potency in this respect was about 10 times that of adrenaline. 5-HT showed many pharmacological similarities to adrenaline and noradrenaline; thus its action in this preparation was abolished by dihydroergotamine and enhanced by cocaine. The same ratio between the potency of 5-HT and adrenaline has been demonstrated in the lung vessels of the dog and the cat by Ginzel and Kottegoda (1953).In the experiments here the action of 5-HT on the placenta has been studied further and special consideration has been given to a series of drugs known to antagonize the actions of 5-HT in other preparations. Since the umbilical vessels do not receive any nerve supply (Schmitt, 1922;Guarna, 1934) it was felt that a study of 5-HT antagonists in this preparation might yield information of interest concerning the pharmacological mechanisms involved. METHODSHuman placentae were obtained from the hospital as soon as possible after delivery.

The Effects of Antimigraine Drugs on the Vascular Responses by-5-Hydroxytryptamine and Related Biogenic Substances on the External Carotid Bed of Dogs: Possible Pharmacological Implications to Their Antimigraine Action

“…Only ergotamine produced a dose dependent blockade and even reversal of 5-HT-induced vasoconstriction; methysergide had some action alone in the two highest dose-range while cyproheptadine lacked any anti-5-HT action in this bed. This is a surprising finding in view of earlier studies on the other vascular beds where the effects of 5-HT are antagonized by typical anti-5-HT agents (see 6,19,[34][35][36] ).…”

“…Only ergotamine produced a dose dependent blockade and even reversal of 5-HT-induced vasoconstriction; methysergide had some action alone in the two highest dose-range while cyproheptadine lacked any anti-5-HT action in this bed. This is a surprising finding in view of earlier studies on the other vascular beds where the effects of 5-HT are antagonized by typical anti-5-HT agents (see 6,19,[34][35][36] In our recent studies with mianserin, 37 we had also noted that this compound, while effectively antagonizing the action of 5-HT on several vascular and non-vascular smooth muscles, did not possess anti-5-HT effect in the external carotid bed. Furthermore, it is interesting to remark that ergotamine, which usually has a very weak anti-5-HT action as compared to LSD, BOL, methysergide or cyproheptadine (see 17,18,36,38,39 ), approaches in activity to that of BOL in the rabbits' ear artery, a branch of external carotid artery.…”