Down-regulation of bombesin binding to guinea-pig pancreatic acinar cells during homologous desensitization.

1. [125I]-Tyr4-bombesin exhibited saturable binding to pancreatic acinar cells. 2. Preincubation of cells at 37 degrees C with 0.03 nM-1 microM-bombesin for 10 min followed by acid or neutral washes reduced subsequent binding of [125I]-Tyr4-bombesin in a concentration-dependent manner by up to 90%. 3. In cell suspensions, bombesin raised the cytoplasmic Ca2+ concentration ([Ca2+]i) and the [Ca2+]i response was reduced by pre-exposure to the agonist. 4. In individual superfused cells, bombesin at 1 nM normally caused a large [Ca2+]i transient followed by sustained [Ca2+]i oscillations. The cells exhibited a variable degree of desensitization when subsequently exposed to higher agonist concentrations. 5. Preincubation with bombesin for 10 min caused a concentration-related reduction of subsequent amylase responses to bombesin. 6. Down-regulation of receptor binding is a rapid phenomenon during bombesin exposure explaining, at least partially, tachyphylaxis of [Ca2+]i and amylase responses.