Galanin, a recently characterized neuropeptide, lowers basal plasma canine insulin levels and inhibits plasma canine insulin responses to parenteral administration or oral ingestion of nutrients. This study determined the effect of galanin on the recognized insulin secretagogue effects of selected hormonal, neuropeptidal, and pharmacological agents in five conscious dogs. Bolus injections of cholecystokinin, the glucose-dependent insulinotropic polypeptide, and glucagon during saline infusions resulted in prompt elevation of plasma insulin levels (peak values, respectively: 57.8 +/- 14.6 microU/ml, 39.0 +/- 9.8 microU/ml, 60.8 +/- 14.4 microU/ml) but insulin responses after administration of these hormones during galanin infusions were statistically significantly blunted (peak values, respectively: 10.8 +/- 3.5 microU/ml, 3.0 +/- 2.8 microU/ml, 8.8 +/- 2.8 microU/ml). Bolus injection of the gastrin-releasing polypeptide, a neuropeptide, during saline infusions resulted in a peak plasma insulin level of 28.2 +/- 8.6 microU/ml but, during galanin infusions, the maximum level attained was significantly lower at 3.4 +/- 2.0 microU/ml. Similarly, tolbutamide administration during saline infusions elevated plasma insulin levels to a peak value of 28.6 +/- 6.2 microU/ml but during galanin infusions, the peak value seen after tolbutamide administration was 4.8 +/- 1.6 microU/ml. Hence, in the conscious dog, galanin effectively inhibits insulin secretion induced by hormones (cholecystokinin, glucose-dependent insulinotropic polypeptide, glucagon), a neuropeptide (gastrin-releasing polypeptide), and a pharmacological agent (tolbutamide). The results from the present and previous studies demonstrate that galanin has a broad spectrum of inhibitory activity on the beta-cell and suggest that it acts on a fundamental step in the insulin secretory process.