VIP receptor activity during HT29-18 cell differentiation and rat intestinal development.

In undifferentiated clonal HT29-18 cells, VIP produced an important (17-fold) and persistent increase in cyclic AMP generation for 10 min. This activation measured at 37 degrees C in the absence of IBMX was transient for 2 min and was considerably reduced (4-fold increase) in enterocyte-like cells. Retrodifferentiation of HT29-18 cells (after substitution of galactose for glucose) resulted in a partial reversion of VIP receptor activity. Cyclic AMP levels reached a peak value at 1 min but remained elevated over basal values for 10 min. Similarly, maturation of intestinal mucosae in 19-day-old rat fetuses and 5 day-old rats was accompanied by a remarkable reduction of VIP receptor activity. Cyclic AMP phosphodiesterase, adenylate cyclase activities and VIP receptor desensitization might explain this phenomenon. In contrast, the potency of VIP and the pharmacological properties of the VIP receptor are unchanged. We therefore assume that VIP receptor activity is an indicator of intestinal cell differentiation and we suggest that this neuropeptide may be a regulator of the normal and tumoral development of the intestinal mucosae in man and rat.