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Prostaglandins and serotonin: Nonpeptide diarrheogenic hormones

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Abstract

Prostaglandins and serotonin are vasoactive compounds with profound effects on the gastrointestinal tract. Both cause inhibition of gastric acid secretion (although serotonin stimulates gastric pepsin secretion), stimulation of intestinal motility, and conversion of small intestinal mucosa from absorption to secretion of water and electrolytes. Their effects on pancreatic and biliary function are still not clear.

Although prostaglandins appear to elicit their effects primarily by a paracrine mode of action, and serotonin is primarily a neurotransmitter (neurocrine), it is clear that even under normal conditions both can function as humoral agents. For example, we have shown that serotonin plays a physiologic role as a humoral inhibitor of gastric acid secretion. However, the effects of these agents become more pronounced in patients with humorally mediated diarrheogenic syndromes. Serotonin (and related indoles, particularly 5-hydroxytryptophan) has been firmly implicated as a cause of diarrhea in patients with carcinoid syndrome; our recent studies suggest that the diagnosis can be more effectively made by measuring circulating immunoreactive serotonin concentrations than urinary excretion of 5-HIAA; that some circulating serotonin escapes hepatic inactivation and, thus, large intestinal tumors can cause carcinoid syndrome in the absence of hepatic metastases; and that large amounts of serotonin are produced by some noncarcinoid diarrheogenic tumors, including medullary carcinomas of the thyroid and tumors associated with the WDHA syndrome. A large number of tumors of probable neural crest origin, including medullary thyroid carcinoma, carcinoids, and tumors associated with the WDHA syndrome, secrete large amounts of prostaglandins, particularly PGE2. The clinical response of at least some of the patients harboring these tumors to inhibitors of prostaglandin synthesis (particularly indomethacin) suggests that prostaglandins play a role in the etiology of these diarrheogenic syndromes.

Résumé

Les prostaglandines et la sérotonine sont des substances vaso-actives qui exercent un effet important sur le tube digestif. Toutes deux inhibent la sécrétion gastrique d'acide (bien que la sérotonine stimule la sécrétion de pepsine). Toutes deux stimulent la motilité intestinale et transforment l'activité d'absorption de la muqueuse intestinale en sécrétion d'eau et d'électrolytes. Leurs effets sur les fonctions biliaires et pancréatiques ne sont pas encore bien définis.

Les prostaglandines semblent agir surtout par un effet paracrine et la sérotonine est principalement un neurotransmetteur (neurocrine). Mais il est clair que, même dans des conditions normales, ces deux substances peuvent agir comme agents humoraux. Nous avons, par exemple, montré que la sérotonine joue un rôle physiologique comme inhibiteur humoral de la sécrétion gastrique d'acide. Cependant, les effets de ces substances sont les plus nets chez les malades atteints de syndromes diarréiques d'origine humorale. La sérotonine (et des indoles de la même famille, en particulier le 5-hydroxytryptophane) semble clairement étre cause de diarrée dans le syndrome carcinoïde. Nos études récentes suggèrent que le diagnostic peut être mieux établi par la mesure des concentrations circulantes de sérotonine immunoréactive que par l'excrétion urinaire de 5-HIAA et qu'une partie de la sérotonine circulante échappe à l'inactivation hépatique. Ainsi, de volumineuses tumeurs intestinales peuvent causer un syndrome carcinoïde en l'absence de métastases hépatiques et des quantités importantes de sérotonine sont produites par des tumeurs diarrhéogènes non carcinoïdes, telles que carcinome médullaire de la thyroïde et tumeurs associées au syndrome WDHA. Bon nombre de tumeurs dont l'origine est probablement la crête neurale—carcinome médullaire de la thyroïde, tumeurs associées au syndrome WDHA, par exemple—secrètent des quantités importantes de prostaglandines, en particulier de PGE2. La réponse clinique de certains malades atteints de ces types de tumeurs aux inhibiteurs de la synthèse des prostaglandines, en particulier l'indométhacine, suggère que les prostaglandines jouent un rôle dans l'étiologie de ce syndrome diarrhéogène.

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    Bernard M. Jaffe M.D.

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Jaffe, B.M. Prostaglandins and serotonin: Nonpeptide diarrheogenic hormones. World J. Surg. 3, 565–577 (1979). https://doi.org/10.1007/BF01654761

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