Beta(β)3-adrenergic receptors in human pancreatic islet and duodenal somatostatin neuroendocrine cells

Background: We previously localized beta(3)-adrenergic receptors immunohistochemically in human gastrointestinal smooth muscle and incidently found a population of human pancreatic islet cells and duodenal epithelial neuroendocrine cells that also expressed beta(3)-adrenergic receptors. Aim: To identify the nature of the islet and duodenal cells that stained positive for beta(3)-adrenergic receptors. Methods: Paraffin sections of human pancreas and duodenum and Chinese hamster ovary cells transfected with the human beta(3)-adrenergic receptor were immuno-stained for beta(3)-adrenergic receptors using an affinity-purified rabbit polyclonal antibody (anti-P12) raised against a 15 amino acid sequence (P12) of the human receptor. Immunohistochemical staining for the receptor was carried out in the presence and absence of P12 peptide and both somatostatin 14 and 18 peptides. beta(3)-adrenergic receptor-stained sections were also double-immunostained with anti-insulin, -glucagon, -somatostatin and -pancreatic polypeptide antibodies. Results: A subpopulation of human pancreatic islet cells and duodenal epithelial cells expressed positive cytoplasmic beta(3)-adrenergic receptor immunostaining. Using distribution and double-staining techniques, these cells were found to be somatostatin-positive D cells but not A or B cells. The positive staining of D cells with anti-P12 antibody was inhibited by prior incubation of the antibody with P12 peptide but not somatostatin-14 or -28 peptides. Pancreatic vascular smooth muscle and duodenal vascular and non-vascular smooth muscle also stained with anti-P12 antibody. Transfected Chinese hamster ovary cells showed positive membrane staining. Conclusion: We have identified a population of neuroendocrine cells in the human pancreas and duodenum that express beta(3)-adrenergic receptors. These cells appear to be somatostatin D cells.