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Department of Pediatric Immunology, University Hospital for Children and Youth "Het Wilhelmina Kinderziekenhuis" (A.K., C.J.H.), and the Department of Clinical Immunology, University Hospital (R.E.B.) Utrecht, The Netherlands
Abstract
Lymphocytes are now recognized as an extrapituitary source of neuropeptides, such as the opioid peptide β- endorphin. In the present paper the intracellular signalling pathways involved in regulation of the secretion of immunoreactive (ir) β-endorphin by human peripheral blood mononuclear cells are described. Activation of protein kinase-C with a phorbol ester rapidly induces secretion of ir-β-endorphin by T-cells as well as by the non-T cell fraction. Stimulation of protein kinase- A by the addition of (Bu)2cAMP to T-cells or non-T-cells can also induce the secretion of ir-jS-endorphin by these cells.
Investigation of the effect of different mitogens or antigen on ir-β-endorphin secretion by lymphocytes revealed that the nature of the stimulus determines the kinetics of the response and the responding cell type. Induction of ir-β-endorphin secretion by T-cells after stimulation with a T-cell mitogen is relatively fast; it can be observed within 3 h. In contrast, the response of the non-T-cell fraction to, for example, stimulation with (Bu)2cAMP can only be observed after 18 h of culture. Evidence will be presented that the fast response is mediated via protein kinase-C activation. The response observed after 18 h can be mediated via protein kinase-C as well as protein kinase-A activation. (Endocrinology 128: 765–770, 1991)
Received August 20, 1990.
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