Differences in Ca(2+) signaling underlie age-specific effects of secretagogues on colonic Cl(-) transport.

Taurodeoxycholic acid (TDC) stimulates Cl(-) transport in adult (AD), but not weanling (WN) and newborn (NB), rabbit colonic epithelial cells (colonocytes). The present study demonstrates that stimuli like neurotensin (NT) are also age specific and identifies the age-dependent signaling step. Bile acid actions are segment and bile acid specific. Thus although TDC and taurochenodeoxycholate stimulate Cl(-) transport in AD distal but not proximal colon, taurocholate has no effect in either segment. TDC increases intracellular Ca(2+) concentration ([Ca(2+)](i)) in AD, but not in WN and NB, colonocytes. In AD cells, TDC (5 min) action on Cl(-) transport needs intra- but not extracellular Ca(2+). NT, histamine, and bethanechol increase Cl(-) transport and [Ca(2+)](i) in AD, but not WN, distal colonocytes. However, A-23187 increased [Ca(2+)](i) and Cl(-) transport in all age groups, suggesting that Ca(2+)-sensitive Cl(-) transport is present from birth. Study of the proximal steps in Ca(2+) signaling revealed that NT, but not TDC, activates a GTP-binding protein, Galpha(q), in AD and WN cells. In addition, although WN and AD colonocytes had similar levels of phosphatidylinositol 4,5-bisphosphate, NT and TDC increased 1,4,5-inositol trisphosphate content only in AD cells. Nonresponsiveness of WN cells to Ca(2+)-dependent stimuli, therefore, is due to the absence of measurable phospholipase C activity. Thus delays in Ca(2+) signaling afford a crucial protective mechanism to meet the changing demands of the developing colon.