Substance P-evoked Cl−secretion in guinea pig distal colonic epithelia: interaction with PGE2

Abstract

Interaction between substance P (SP) and PGE2on Cl−secretion in the guinea pig distal colonic epithelia was investigated. A short-circuit current ( Isc) was measured as an index of ion transport. Mucosa preparations deprived of muscle and submucosa of distal colon were mounted in the Ussing flux chamber and treated with TTX and piroxicam to remove the influences of neuronal activity and endogenous PG synthesis, respectively. Although SP (10−7M) itself evoked little increase in Isc, exogenous PGE2concentration dependently enhanced the response of SP. The effect of PGE2on the SP-evoked response was mimicked by forskolin and 8-bromoadenosine cAMP. Depletion of Ca2+from the bathing solution reduced the PGE2-dependent response of SP. Effects of PGE2, SP, and SP in the presence of PGE2on intracellular Ca2+concentration ([Ca2+]i) in isolated crypt cells were measured by the confocal microscope fluorescence imaging system. SP, but not PGE2, temporally evoked an increase in [Ca2+]ibut declined to the baseline within 3 min. A return of the SP-evoked increase in [Ca2+]iwas slower in the presence of PGE2than SP alone. These results suggest that PGE2synergistically enhances SP-evoked Cl−secretion via an interaction between the intracellular cAMP and [Ca2+]iin the epithelial cells. In conclusion, SP and PGE2could cooperatively induce massive Cl−secretion in guinea pig distal colon at epithelial levels.