Mitogenic and antimitogenic effects of pituitary adenylate cyclase-activating polypeptide (PACAP) in adult rat chromaffin cell cultures
| Autor: | Arthur S. Tischler, Robyn Gray, Jocelyn C. Riseberg |
|---|---|
| Rok vydání: | 1995 |
| Předmět: |
endocrine system
medicine.medical_specialty Indoles Phosphodiesterase Inhibitors medicine.medical_treatment Biology Internal medicine medicine Animals Nerve Growth Factors Protein kinase A Protein Kinase Inhibitors Cells Cultured Sulfonamides Cell growth General Neuroscience Growth factor Neuropeptides Isoquinolines Rats Inbred F344 Oxindoles Rats Pyridazines Pituitary adenylate cyclase-activating peptide Nerve growth factor medicine.anatomical_structure Endocrinology Bromodeoxyuridine Chromaffin System Chromaffin cell Catecholamine Pituitary Adenylate Cyclase-Activating Polypeptide Female Mitogens Adrenal medulla Cell Division hormones hormone substitutes and hormone antagonists medicine.drug |
| Zdroj: | Neuroscience Letters. 189:135-138 |
| ISSN: | 0304-3940 |
| DOI: | 10.1016/0304-3940(95)11472-9 |
| Popis: | The neurotransmitter, pituitary adenylate cyclase-activating polypeptide (PACAP), is present in the rat adrenal medulla and is a potent stimulus for catecholamine secretion. Previous studies have suggested that neurally derived signals stimulate proliferation of chromaffin cells in adult rats. To determine whether PACAP might be involved in mitogenic signalling, its effects on bromodeoxyuridine incorporation were studied in adrenal medullary cell cultures from adult female rats. Both PACAP 27 and PACAP 38 are able to stimulate proliferation of adult rat chromaffin cells in vitro, either alone or in conjunction with PMA, an activator of protein kinase C. BrdU-labelled nuclei are observed in both epinephrine and norepinephrine cells, and proliferation of both cell types is stimulated by the same concentrations of PACAP that elicit secretion of catecholamines. The mitogenic effects of PACAP are potentiated by indolidan, a phosphodiesterase inhibitor known to cause pheochromocytomas in rats, and are inhibited by H-89, an inhibitor of protein kinase A. Mitogenic concentrations of PACAP inhibit mitogenic effects of nerve growth factor. These findings support the hypothesis that neurally derived signals regulate chromaffin cell proliferation in adult rats. Indolidan and a variety of non-genotoxic agents that cause pheochromocytomas in rats may do so indirectly by increasing neurally mediated chromaffin cell turnover. The antagonism between PACAP and NGF suggests that neurotransmitters may supersede growth factors in regulating chromaffin cell proliferation during development by suppressing or co-opting portions of growth factor signaling pathways. |
| Databáze: | OpenAIRE |
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