Inositol trisphosphate-linked calcium mobilization couples substance P receptors to conductance increase in a rat pancreatic acinar cell line.

The action of substance P (SP) on a rat pancreatic acinar cell line, AR4-2J, was examined using the whole-cell voltage-clamp technique. Pressure application of SP evoked inward currents accompanying increased membrane conductance. The SP-induced response was suppressed in Ca2+-free or low-Na+ solution. Treatment of cells with caffeine or A23187 produced a transient inward current and depressed the response to SP. Intracellular application of inositol 1,4,5-trisphosphate or guanosine 5'-O-(3-thiotriphosphate) elicited sustained inward currents and suppressed the SP-induced response. The results suggest that activation of SP receptors stimulates the formation of inositol phosphates via a guanine nucleotide-binding protein and leads to the rise in intracellular Ca2+, thereby activating a cation conductance in AR4-2J cells.