SIGNAL-TRANSDUCTION PATHWAYS ASSOCIATED WITH CONTRACTION DURING DEVELOPMENT OF THE FELINE GASTRIC ANTRUM

Background & Aims: Unlike adult antral cells, feline newborn antral ce lls are unable to contract in response to agonists in the absence of e xtracellular calcium or in response to exogenous inositol 1,4,5-tripho sphate (IP3) after permeabilization, Changes in intracellular pathways that are associated with these differences were examined. Methods: In adult and kitten antrum isolated smooth muscle cell contraction, leve ls of 1,2-diacylglycerol (DAG) and IP3 were assessed in response to ch olecystokinin (CCK). Results: CCK-induced contraction was transient in the adult and sustained in the kitten, U73122 blocked contraction in adult antral cells but not kitten antral cells, In adult antral tissue , CCK (10(-7) mol/L) caused an early transient increase in the level o f DAG, whereas in the newborn antrum, CCK (10(-7) mol/L) caused a sust ained increase in the DAG level for up to 4 minutes, IP3 showed an ear ly increase in both age groups, Newborn contraction is associated with an initial increase in IP3 and sustained elevation of DAG levels, whe reas in adult antral cells, there is a transient increase in both IP3 and DAG, Conclusions: The relative inaccessibility of intracellular ca lcium stores in the newborn is associated with age-related differences in signal transduction pathways.