Prostaglandins and serotonin: Nonpeptide diarrheogenic hormones

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.

The inhibitory effects of 5‐hydroxytryptamine on gastric acid secretion by the rat isolated stomach

“…The majority of these studies have been in dog or rat (for review see Thompson, 1971;Jaffe, 1979). 5-HT is found throughout the gut and especially in the stomach and duodenum but a clear role for endogenous 5-HT in the normal regulation of gastric acid secretion has not been established.…”

Carcinoid syndrome from a carcinoid tumor of the pancreas without liver metastases: A case report and literature review

“…A search in Pubmed (http://www.ncbi.nlm.nih.gov/pubmed) and Scopus (http://www.scopus.com/) using the terms 'carcinoid syndrome', 'carcinoid syndrome without liver metastasis', 'gastrointestinal carcinoid tumor' and 'carcinoid tumor of the pancreas' revealed only one previous study concerning a CTP with CS without liver metastases (6). In all other cases with CS without liver metastases, the carcinoid tumor location was either the intestine (7-10) or was not stated (11,12).…”

Antidiarrheal mechanism ofCarpolobia lutealeaf fractions in rats

“…The prostaglandins thus released promote vasodilatation, smooth muscle contraction, and mucus secretion in the small intestines (Pierce et al, 1971;Robert, 1973). The prostaglandins of the E series are considered to be good diarrheogenic agents in experimental animals as well as in human beings (Jaffe, 1979). The inhibitors of prostaglandins biosynthesis are therefore considered to delay the castor oil-induced diarrhea (Pierce et al, 1971).…”