A novel gastrin inhibitor in sheep abomasal contents : a thesis presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Physiology at Massey University, Palmerston North, New Zealand

Abstract

Gastrin secretion was studied in vitro and in vivo in response to pharmacological agents and chemicals, as well as abomasal parasites and microbial products. The causes and effects of hypergastrinaemia, along with bacterial numbers and the presence of a gastrin secretion inhibitor in the abomasal contents of sheep infected with Ostertagia circumcincta were studied. The pharmacology of the gastrin secretion from the unparasitised antrum was shown to be similar to that in monogastric animals. In vitro gastrin secretion by ovine antral segments was stimulated by Gastrin Releasing Peptide, carbachol and nicotine, but not adrenaline. Basal gastrin release was unaffected by somatostatin or Vasoactive Intestinal Polypeptide, but these reduced the gastrin response to stimulants. Gastrin secretion was also stimulated by amino acids, ammonia and acetate. Hypergastrinaemia during O. circumcincta infection did not correlate well with decreased food intake or appear to affect parietal cell recovery. Serum gastrin concentrations correlated well with abomasal pH following adult O. circumcincta transplant, but poorly after larval infections. This suggests that other factors, such as inflammation and tissue damage, also affect gastrin secretion during abomasal parasitism. Anaerobic bacterial numbers in abomasal contents increased to near rumen levels when abomasal pH was 3.5 and above, but this did not affect serum gastrin concentrations. An inhibitor of in vitro gastrin secretion also started to appear in abomasal contents of pH3.5 and over, but did not have significant effects on in vitro gastrin secretion unless contents were pH4.5 and over. However, gastrin inhibitory activity in abomasal contents and serum gastrin levels were positively correlated, suggesting abomasal gastrin inhibitory activity has little effect on gastrin secretion in vivo. Three competing factors were present in rumen fluid and rumen incubates: an inhibitor and a stimulant of secretion and an elimination factor. The stimulant was resistant to acid degradation, had a molecular weight below 3000 Mr and was hydrophilic. Both the elimination factor and the inhibitor were sensitive to acidity and hydrophobic and are likely to be proteinaceous.