Structural requirements for galanin inhibition of pentagastrin-stimulated gastric acid secretion in conscious rats

The effects of rat galanin, together with a number of its N- and C-terminal fragments, on pentagastrin-stimulated gastric acid secretion were studied in conscious rats equipped with chronic gastric fistulas. Similarly to its porcine counterpart studied previously, at a dose of 3 nmol/kg per h rat galanin was a potent inhibitor of gastric acid secretion. The N-terminal fragments, rat galanin-(1-10) and-(1-15), retained about 60% of the inhibitory potency of the whole galanin sequence whilst the C-terminal fragments, rat galanin-(2-29), -(3-29) and -(9-29), were unable to produce significant inhibition over comparable dose ranges. Surprisingly, however, simply acetylating the α-amino group in position 9 of rat galanin-(9-29) restored almost full gastric acid inhibitory activity in a homologous rat model. We speculate that this could be due to a favorable conformational effect on the C-terminal region produced by α-acetylation. These results also suggest that structural features within either the N-terminal or C-terminal regions of rat galanin are able to elicit this particular biological response. One possible explanation for this could be the involvement of more than one rat galanin receptor having different ligand recognition requirements.