Species-specific effects of neurotensin on gallbladder contractionin vitro

Publisher Website
Google Scholar
Abstract
We have previously shown that an in vivoadministration of neurotensin (NT) stimulates contraction of dog gallbladder (GB), but produces dilatation of GB in humans. The objective of this study was to examine the effect of NT on human, dog, guinea pig, and rabbit GB in vitro,in order to delineate direct versus indirect actions of NT in different species and to evaluate the structure-activity relationships of NT. The effect of NT on the canine sphincter of Oddi (SOD) was also examined in vitro.Isolated longitudinal strips of GB from the four species given above and SOD from dogs were suspended in oxygenated Krebs buffer, and the isometric tension responses to various doses of NT, NT 8–13, NT 1–11, and xenopsin (XP) were determined. All the NT homologs, except NT 1–11, stimulated contraction of the dog GB and SOD in a dose-dependent manner. NT also caused dose-related stimulation of GB contraction from guinea pigs but did not stimulate or depress the contractile activity of human and rabbit GB strips. These results suggest that NT action on GB contraction is species-specific. Tetrodotoxin did not modify the contraction of dog GB and SOD in response to NT, indicating that NT mediates its contractile effects directly. The relaxing effect of NT on GB of humans in vivo,as previously reported by us, thus appears to be an indirect action. The fact that structural changes in the NT molecule resulted in marked changes in the biological activity of NT on GB activity in dogs indicates that the effects of NT on dog GB contraction are probably mediated through binding of NT to specific receptors that requires both the C-terminal amino group and the two C-terminal amino acids to produce a contractile response. Based on these results, we suggest that NT may participate in the regulation of GB and SOD contraction in dogs.