Date of Award

5-1-1978

Degree Type

Dissertation

Degree Name

Ph.D.

Department

Department of Biology

First Advisor

Gordon J. Leitch

Abstract

The ligated ileal loop of the rabbit is a widely accepted model for the study of human diarrheal diseases. After exposing the ileal loop to cholera enterotoxin, the net absorptions of water, sodium and chloride changed to secretions, and there was an increase in bicarbonate and mucus secretions. Cholera enterotoxin-induced water and electrolyte secretion reached maximum values in the second hour after toxin exposure and remained there throughout the remaining hours of the experiment. In contrast, mucus secretion was maximum in the second hour and gradually declined thereafter. Luminal fluid viscosity was used to assess mucus secretion by measuring viscosity at a constant shear rate, after first normalizing the loop fluid volume to loop length. There was good correlation between the pattern of luminal fluid viscosity and the pattern of secretion of non-dialyzable hexose, protein and sialic acid, which are indicators of mucin glycoprotein. Prostaglandin had qualitatively the same effect on water, electrolyte and mucus secretion as cholera enterotoxin. Drugs that inhibit experimental diarrhea, such as cycloheximide, colchicine and cytochalasin B inhibited mucus secretion at doses that did not inhibit water and electrolyte secretion. Acetazolamide inhibited water and electrolyte secretion but only delayed mucus secretion. It is concluded on the basis of this study that: 1) water and electrolyte secretion can be separated from mucus secretion in experimental diarrhea; 2) mucus secretion is more sensitive to inhibition of protein synthesis , microtubule disruption and microfilament disruption than is water and electrolyte secretion and 3) the use of luminal fluid viscosity as a measure of mucus secretion provides rapid, on-line information about mucus secretion in contrast to the more lengthy biochemical and immunological methods.

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