Increased intestinal non-substance P tachykinin concentrations in malignant midgut carcinoid disease

Abstract

Background: Diarrhoea is an important feature of the carcinoid syndrome, and various agents which may be released from carcinoid tumours have been considered to contribute pathophysiologically. The aim of the present study was to determine luminal concentrations of possible chemical mediators in an uninvolved small intestinal segment using a two-balloon six-channel tube in nine patients with malignant midgut carcinoid disease.

Methods: All patients were treated with interferon and/or octreotide to alleviate the most severe flush. Ion transport was measured during luminal perfusion and luminal perfusate concentrations of calcitonin gene-related peptide, neurotensin, prostaglandin E (PGE)2, neuropeptide Y, somatostatin, vasoactive intestinal polypeptide, substance P and other tachykinins (neurokinin A, neurokinin B, neuropeptide K, eledoisin) were determined by separate assays.

Results: Carcinoid patients showed decreased absorption of Cl-, Na+, K+ and water and increased luminal content of non-substance P tachykinins to 424.5 fmol/cm per h, compared with 255.5 fmol/cm per h in control subjects. There were also increased luminal concentrations of PGE2, commonly claimed as a more general mediator of diarrhoea.

Conclusions: The observed increase in intestinal tachykinins may involve extended activity from tachykinin-containing intrinsic neurones in the enteric nervous system, contributing to enhanced intestinal motility and secretory diarrhoea in patients with carcinoid syndrome.