Preponderance of /8-Adrenergic Binding Sites in Pancreatic Islet Cells of the Rat

Although the a- and /3-adrenergic receptors have opposing effects on insulin secretion, the inhibitory in-fluence of a-receptors appears to predominate. To de-termine if this was due to differences in number and affinity of receptors, isolated rat pancreatic islet cells were incubated with [3H]-dihydroalprenolol and [3H]-di-hydroergocryptine as ligands for /3- and a-adrenergic binding sites. It was found that the number of /3-adre-nergic binding sites was 143 fmol/mg islet protein with a Kd = 0.57 nM. The number of a-adrenergic binding sites was 53 fmol/mg protein with a Kd = 0.26 nM. Thus, there are 2.7 times as many /3-adrenergic bind-ing sites as a-binding sites, and neither binding site number nor affinity is responsible for the predominant influence of the a-adrenergic receptors. DIABETES 30:172-174, February 1981. It is generally accepted that secretion of insulin can bemodulated by the sympathetic nervous system.1 Stimu-lation of a-receptors inhibits insulin release, while stim-ulation of/3-receptors increases it. Epinephrine is known to stimulate both a- and /3-adrenergic receptors, but when infused in whole animals its predominant effect is to inhibit insulin secretion.2"4 Since this effect is blocked by phentol-amine,3 the inhibitory effect of epinephrine is ascribed to an action on a-receptors. It is of interest, therefore, to deter-mine why the inhibitory effect of a-receptors on insulin se-cretion predominates over that of the /3-receptors. One pos-sibility is that there is a larger number of a-receptors on the pancreatic islet cells. The present study uses appropriate ligands to determine the density and affinity of a- and /3-adrenergic binding sites on pancreatic islet cells, and it was found, surprisingly, tha