title: The β isoenzyme of Ca(2+)/calmodulin-dependent kinase type II as possible mediator of somatostatin functions in pituitary tumour cells.
abstract: Somatostatin or somatostatin release inhibiting factor (SRIF) analogues are indicated for the treatment of somatotropinomas that hypersecrete growth hormone (GH). Indeed, SRIF inhibits intracellular Ca(2+) concentration ([Ca(2+)](i)), thus allowing the inhibition of GH secretion. In the present study, our hypothesis was that Ca(2+)/calmodulin-dependent kinase type II (CaMKII), a multifunctional serine/threonine protein kinase, is part of those signalling mechanisms mediating SRIF functions. All four CaMKII isoenzymes (termed α, β, γ and δ) are expressed in rat somatotroph GC cells, although only CaMKIIβ is inhibited by SRIF at both mRNA and protein levels. Similarly to SRIF, the specific knockdown of CaMKIIβ by RNA interference induces a decrease of [Ca(2+)](i). The effects of SRIF and those of CaMKIIβ knockdown are non-additive. These results are confirmed by the pharmacological blockade of CAMKII. We also observed that, similarly to SRIF, the specific knockdown of CaMKIIβ induces a decrease of both GH content/secretion. These results raise the hypothesis that CaMKIIβ may mediate, at least in part, the SRIF-induced control of [Ca(2+)](i). In addition, CaMKIIβ seems to play a positive role in maintaining the exocytosis of GH. Our data provide a framework for better elucidating the pathophysiological role of SRIF transduction network in somatotropinomas.
authors.affiliation: Department for Innovation in Biological, Agro-food and Forest systems, University of Tuscia, Viterbo, Italy. d.cervia@unitus.it
authors.forename: Davide
authors.initials: D
authors.lastname: Cervia
mesh_terms: D000818:Animals; D002118:Calcium / Q000737:chemistry; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism*; D017931:DNA Primers / Q000235:genetics; D013006:Growth Hormone / Q000378:metabolism; D007124:Immunoenzyme Techniques / Q000379:methods; D007527:Isoenzymes / Q000737:chemistry*; D010911:Pituitary Neoplasms / Q000378:metabolism*; D020033:Protein Isoforms; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013004:Somatostatin / Q000378:metabolism*
chemical_list: D017931:DNA Primers; D007527:Isoenzymes; D020033:Protein Isoforms; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D013004:Somatostatin; D013006:Growth Hormone; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D002118:Calcium