G Protein Receptors 7 and 8 Are Expressed in Human Adrenocortical Cells, and Their Endogenous Ligands Neuropeptides B and W Enhance Cortisol Secretion by Activating Adenylate Cyclase- and Phospholipase C-Dependent Signaling Cascades
| Autor: | A. Ziolkowska, G. Mazzocchi, G.P. Rossi, G. G. Nussdorfer, L. K. Malendowicz, Piera Rebuffat |
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| Rok vydání: | 2005 |
| Předmět: |
Receptors
Neuropeptide Cortisol secretion endocrine system medicine.medical_specialty Hydrocortisone G protein Endocrinology Diabetes and Metabolism Clinical Biochemistry Biology Biochemistry Receptors G-Protein-Coupled Endocrinology Zona fasciculata Internal medicine Cyclic AMP medicine Humans RNA Messenger Aldosterone DNA Primers Phospholipase C Reverse Transcriptase Polymerase Chain Reaction Adrenal cortex Neuropeptides Biochemistry (medical) Steroid 17-alpha-Hydroxylase Neuropeptide W Zona Reticularis medicine.anatomical_structure Zona glomerulosa Type C Phospholipases Adrenal Cortex Steroid 11-beta-Hydroxylase Zona Glomerulosa Zona Fasciculata Zona reticularis Adenylyl Cyclases Signal Transduction |
| Zdroj: | The Journal of Clinical Endocrinology & Metabolism. 90:3466-3471 |
| ISSN: | 1945-7197 0021-972X |
| DOI: | 10.1210/jc.2004-2132 |
| Popis: | Neuropeptides B and W (NPB and NPW) are regulatory peptides that act via two subtypes of G protein-coupled receptors, named GPR7 and GPR8. RT-PCR demonstrated the expression of these receptors in both zona glomerulosa and zona fasciculata-reticularis (ZF/R) cells of the human adrenal cortex. NPB and NPW did not affect aldosterone secretion from dispersed zona glomerulosa cells but enhanced cortisol production from ZF/R cells, NPB being more effective than NPW. NPB evoked sizable cAMP and inositol triphosphate responses from ZF/R cells, which were abrogated by the adenylate cyclase inhibitor SQ-22536 and the phospholipase C inhibitor U-73122, respectively. Cortisol response to NPB was lowered by either SQ-22536 and the protein kinase (PK) A inhibitor H-89 or U-73122 and the PKC inhibitor calphostin-C and abolished by the simultaneous exposure to H-89 and calphostin-C. NPW elicited only a rise in cAMP production from dispersed ZF/R cells, and its cortisol response was suppressed by both SQ-22536 and H-89. PreproNPB and preproNPW mRNAs were detected in human adrenal cortexes. We conclude that: 1) NPB and NPW exert a secretagogue action on human ZF/R cells, probably acting in an autocrine-paracrine manner; and 2) the effect of NPB is mediated by both the adenylate cyclase/PKA and the phospholipase C/PKC cascades, whereas that of NPW involves only the activation of the former signaling pathway. |
| Databáze: | OpenAIRE |
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