Immunocytochemistry was carried out on sections of rat pancreas to localize the expression of glutamate receptor subunits and the major pancreatic peptide hormones. Glutamate receptor expression was concentrated in pancreatic islets, and each islet cell type expressed different neuronal glutamate receptors of the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) and kainate classes. AMPA receptor subunits were expressed in alpha, beta, and pancreatic polypeptide cells, whereas kainate receptors were found predominantly in alpha and delta cells. Patch clamp electrophysiology was used to measure the functional properties of islet cell glutamate receptors, L-glutamate and other glutamate receptor agonists evoked currents in islet cells that were blocked by the selective AMPA receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione and potentiated by cyclothiazide in a manner indistinguishable from that of neuronal AMPA receptors. Activation of islet cell AMPA receptors produced steady-state cation currents that depolarized the cells an average of 20.7 +/- 5.4 mV (n = 6), Currents mediated by functional kainate receptors were also observed in a line of transformed pancreatic alpha cells, Thus, L-glutamate probably regulates islet physiology via actions at both AMPA and kainate receptor classes, The pattern of receptor expression suggests that glutamate receptor activation may have multiple, complex consequences for islet physiology.
