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The expression and function of histamine H 3 receptors in pancreatic beta cells
Author(s) -
Nakamura T,
Yoshikawa T,
Noguchi N,
Sugawara A,
Kasajima A,
Sasano H,
Yanai K
Publication year - 2014
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/bph.12429
Subject(s) - receptor , histamine , endocrinology , medicine , histamine receptor , biology , histamine h1 receptor , calcium in biology , creb , agonist , beta cell , signal transduction , microbiology and biotechnology , chemistry , insulin , biochemistry , islet , gene , transcription factor , antagonist
Background and Purpose Histamine and its receptors in the CNS play important roles in energy homeostasis. Here, we have investigated the expression and role of histamine receptors in pancreatic beta cells, which secrete insulin. Experimental Approach The expression of histamine receptors in pancreatic beta cells was examined by RT‐ PCR , W estern blotting and immunostaining. Insulin secretion assay, ATP measurement and calcium imaging studies were performed to determine the function and signalling pathway of histamine H 3 receptors in glucose‐induced insulin secretion ( GIIS ) from MIN6 cells, a mouse pancreatic beta cell line. The function and signalling pathway of H 3 receptors in MIN6 cell proliferation were examined using pharmacological assay and W estern blotting. Key Results Histamine H 3 receptors were expressed in pancreatic beta cells. A selective H 3 receptor agonist, imetit, and a selective inverse H 3 receptor agonist, JNJ ‐5207852, had inhibitory and facilitatory effects, respectively, on GIIS in MIN6 cells. Neither imetit nor JNJ ‐5207852 altered intracellular ATP concentration, or intracellular calcium concentration stimulated by glucose and KCl , indicating that GIIS signalling was affected by H 3 receptor signalling downstream of the increase in intracellular calcium concentration. Moreover, imetit attenuated bromodeoxyuridine incorporation in MIN6 cells. The phosphorylation of cAMP response element‐binding protein ( CREB ), which facilitated beta cell proliferation, was inhibited, though not significantly, by imetit, indicating that activated H 3 receptors inhibited MIN6 cell proliferation, possibly by decreasing CREB phosphorylation. Conclusions and Implications Histamine H 3 receptors were expressed in mouse beta cells and could play a role in insulin secretion and, possibly, beta cell proliferation.