Phospholipase C and src tyrosine kinases mediate neurotensin-stimulated Cl- secretion in rabbit proximal colon

Calcium-dependent secretagogues, such as neurotensin, stimulate age-dependent chloride transport in rabbit distal colonocytes, but their action in the proximal colon is unknown. This study examines the effect of neurotensin on chloride transport and its mechanism of action in rabbit proximal colonocytes. Our results show that neurotensin stimulates chloride transport only in adult, and not weanling or newborn, colonocytes. The calcium ionophore A23187 shows similar age dependence, while PGE(2), which acts via cAMP, stimulates transport in all ages. The roles of phospholipase C, tyrosine kinases, and src tyrosine kinases were examined using specific inhibitors, i.e., U73122, genistein, and PP2, respectively. All three agents significantly inhibit neurotensin-stimulated chloride transport in adult colonocytes. In conclusion, this study reports for the first time that neurotensin stimulates chloride secretion in rabbit proximal colonocytes. This is also the first demonstration that neurotensin action exhibits age dependence and is dependent on phospholipase C and src tyrosine kinase activity.