Signalling Pathways Mediating Secretory and Mitogenic Responses to Galanin and Pituitary Adenylate Cyclase-Activating Polypeptide in the 235-1 Clonal Rat Lactotroph Cell Line
| Autor: | Karen O. Akinsanya, David M. Smith, S.R. Bloom, P J Hammond, D. Wynick, W. A. Mufti |
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| Rok vydání: | 1996 |
| Předmět: |
endocrine system
medicine.medical_specialty Endocrinology Diabetes and Metabolism Neuropeptide Galanin Biology Calcium in biology Cell Line Prolactin cell Cellular and Molecular Neuroscience chemistry.chemical_compound Endocrinology Pituitary Gland Anterior Internal medicine Cyclic AMP medicine Animals Inositol Enzyme Inhibitors Estrenes Protein kinase C Phospholipase C Endocrine and Autonomic Systems Neuropeptides Pyrrolidinones Prolactin Rats chemistry Type C Phospholipases Pituitary Adenylate Cyclase-Activating Polypeptide Female Cell Division hormones hormone substitutes and hormone antagonists Signal Transduction |
| Zdroj: | Journal of Neuroendocrinology. 8:457-464 |
| ISSN: | 0953-8194 |
| DOI: | 10.1046/j.1365-2826.1996.04747.x |
| Popis: | The neuropeptides galanin and pituitary adenylate cyclase-activating peptide (PACAP) have been implicated in the physiological regulation of lactotroph function. Using the 235-1 clonal lactotroph rat cell line we have studied the signalling pathways mediating the secretory and mitogenic responses to galanin and PACAP. Both peptides stimulated prolactin release to a similar maximal extent. PACAP (100 nM) stimulated an increase in the proliferation rate of 235-1 cells, but was significantly less effective than 100 nM galanin (161.8 +/- 2.3% vs 296.1 +/- 9.1% of control). PACAP stimulated cAMP accumulation with an ED50 of 3.2 nM, and a maximal effect of almost two-fold at a concentration of 100 nM. Galanin depleted cAMP, by 30% at a concentration of 100 nM. The aminosteroid phospholipase C (PLC) inhibitor U-73122 virtually abolished maximal peptide stimulated prolactin release. Depletion of inositol phosphates or downregulation of protein kinase C reduced maximal peptide stimulated prolactin release from about 260% to about 160% of unstimulated release. Both peptides at a concentration of 100 nM caused a sustained increase in intracellular calcium when incubated with cells for 30 min. These results demonstrate that both peptides stimulate prolactin release and the proliferation rate of 235-1 cells. The most important signalling pathway for prolactin release activated by both peptides is via PLC, although they also regulate cAMP levels, which are increased by PACAP and decreased by galanin. Despite maximal peptide stimulated prolactin release being equal, galanin has a greater mitogenic effect on 235-1 cells than PACAP, raising the possibility that it activates an additional mitogenic signalling pathway. |
| Databáze: | OpenAIRE |
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