Rapid down‐regulation of substance P binding to guinea‐pig pancreatic acinar cells during homologous desensitization.

Binding of 125I‐labelled peptides, cytoplasmic Ca2+ concentration ([Ca2+]i) and amylase release were studied in guinea‐pig pancreatic acinar cells during exposure to substance P (SP), and cholecystokinin octapeptide (CCK‐8). Pre‐incubation of cells at 22 degrees C with 0.03 nM to 1 microM SP for 10 min or at 37 degrees C for 5 min followed by acid or neutral washes reduced subsequent binding of 125I‐Bolton‐Hunter reagent‐labelled SP (125I‐BH‐SP) in a biphasic manner by up to 95%. Incubation at 4 degrees C eliminated high‐affinity binding of 125I‐BH‐SP and concentrations of SP above 1 nM were required for inhibition of subsequent tracer binding. Pre‐incubation of cells at 37 degrees C with 1 nM to 1 microM CCK‐8 for 10 min followed by neutral washes reduced subsequent binding of 125I‐BH‐CCK‐8 by up to 65%. In cell suspensions, the [Ca2+]i response to SP was gradually reduced by pre‐exposure to increasing agonist concentrations from 0.2 to 20 nM. Pre‐incubation with high SP concentrations for 10 min caused profound reduction of subsequent amylase responses to SP, whereas secretion was little affected in corresponding experiments with CCK‐8. Down‐regulation of receptor binding is not important during short exposure to CCK‐8, but it is a pronounced and rapid phenomenon during SP exposure, which explains tachyphylaxis of [Ca2+]i and amylase responses.