Effects of the pesticide amitraz and its metabolite BTS 27271 on insulin and glucagon secretion from the perfused rat pancreas:: Involvement of α2D-adrenergic receptors

The study purpose was to investigate the direct effect of amitraz, a formamidine insecticide/acaricide. and its active metabolite BTS 27271 on insulin and glucagon secretion from the perfused rat pancreas. Amitraz and BTS 27271 (0.01, 0.1, 1, and 10 mu mol/L) inhibited insulin secretion in a concentration-dependent manner. Amitraz increased glucagon secretion at 10 mu mol/L, whereas BTS 27271 increased glucagon secretion at 1 and 10 mu mol/L. Amitraz- and BTS 27271-induced decreases in insulin secretion and increases in glucagon secretion were not abolished during the 10-minute washout period. During the arginine treatment, both amitraz and BTS 27271 groups (0.1, 1. and 10 mu mol/L) had lower insulin secretion and higher glucagon secretion than the control group. Idazoxan, an alpha(2A/2D)-adrenergic receptor (AR) antagonist, prevented the inhibitory effect of amitraz on insulin secretion in a concentration-dependent manner. but prazosin, an alpha(1)- and alpha(2B/2C)-AR antagonist, failed to antagonize the effect of amitraz. These results demonstrate that (1) amitraz and BTS 27271 inhibit insulin and stimulate glucagon secretion from the perfused rat pancreas, (2) amitraz inhibits insulin secretion by activation of alpha(2D)-ARs, since rats have alpha(2D)-. but not alpha(2A)-ARs, and (3) amitraz and BTS 27271 may have a high binding affinity to the alpha(2D)-ARs of pancreatic islets. Copyright (C) 1999 by W.B. Saunders Company.