The gastrointestinal effects of calcitonin and related peptides

Abstract

Possible mechanisms of action of the anti-ulcerogenic properties of the hormone calcitonin and some related peptides have been investigated.
The hypocalcaemic actions and the actions on indomethacin-induced gastric erosions of calcitonin, icatacalcin and calcitonin
gene-related peptide (CGRP) were found to be very different. Whilst calcitonin was shown to have both hypocalcaemic and anti-ulcerogenic actions, katacalcin demonstrated only an hypocalcaemic action, and CGRP showed neither of these actions. The results indicate that anti-ulcerogenic activity is a property of the calcitonin molecule alone and cannot be explained solely by the hypocalcaemic activity of calcitonin.
Methodology was developed to measure the glycoprotein content of the whole stomach as an index of changes in the gastric mucus. Indomethacin significantly reduced the glycoprotein content of the stomach, whilst calcitonin reversed this reduction to near normal levels and carbenoxolone sodium to significantly higher than normal levels. Despite this reversal, carbenoxolone sodium failed to reduce the ulceration produced by indomethacin. In contrast, calcitonin significantly inhibited the indomethacin-induced ulceration. An increase in mucus production alone is therefore insufficient to account for the anti-ulcerogenic effect observed.
Of the several methods of measuring gastric blood flow evaluated, none proved successful under the experimental conditions imposed. Intracerebroventricular injection of low doses of calcitonin produced greater inhibition of indomethacin-induced ulceration than administration of the same dose by the subcutaneous route. The results suggest that following intracerebroventricular calcitonin administration, part of the anti-gastric erosive action must be mediated via the central nervous system, possibly by an action on gastric acid secretion.
Isolated rat stomach studies demonstrated that calcitonin reduced basal hydrogen ion output and also that induced by indomethacin, and pentagastrin in the presence of indomethacin or bile salts. A calcitonin-stimulated increase in bicarbonate secretion may be suggested to explain these results.
A mechanism for the gastrointestinal action of calcitonin is postulated.