A study of some factors influencing the transport of fluid and electrolytes in the canine jejunum

Abstract

The triple-lumen perfusion technique has been used to assess the effects of some regulatory peptides upon the intact canine small bowel. Calcitonin gene-related peptide (CGRP) was administered by intravenous infusion at doses of 2.5, 10 and 50 pmol .kg'1.min'1. The effects upon net jejunal water and electrolyte fluxes, plasma somatostatin concentrations, haemodynamic parameters and pharmacokinetics are described. The highest dose of CGRP produced transient net jejunal water and electrolyte secretion and induced diarrhoea in 4 of the 6 dogs under study. Reasons for the transient nature of the secretory response are discussed. The peptide produced a dose-dependent tachycardia, hypotension and increases in plasma immunoreactive somatostatin. The metabolic clearance rate was significantly decreased at the highest dose of CGRP. All three doses of calcitonin generelated peptide produced plasma immunoreactive peptide levels within the elevated range previously measured in human patients with medullary thyroid carcinoma. Calcitonin gene-related peptide may play a significant role in the pathogenesis of secretory diarrhoea in this condition. It is speculated that the release of endogenous somatostatin produced by infusion of CGRP may contribute to the transient secretory nature of net jejunal water and electrolyte fluxes because somatostatin (SS) inhibits intestinal secretion. The mechanism by which this is achieved is unknown. Effects of somatostatin upon permeability of the jejunal mucosa and upon osmotically-induced water secretion in response to dietary carbohydrates were studied using the triple-lumen perfusion technique with intraluminal hypertonic solutions of Urea, Creatinine, Mannitol and Glucose. SS was administered by intravenous infusion at a dose of 240 pmol.kg'1.h-1 with an initial bolus dose of 240 pmol.kg'1. The effects upon permeability parameters, net jejunal water and electrolyte fluxes and haemodynamic parameters were assessed. Hypertonic perfusates of mannitol, creatinine and urea stimulated osmotically-induced secretion and caused plasma osmolality and solute concentrations to increase significantly.