Modulations of Early and Late Secretory Processes by Activation of Protein Kinases in the Rat Adrenal Medulla
| Autor: | Akira Warashina |
|---|---|
| Rok vydání: | 1998 |
| Předmět: |
Male
Nicotine medicine.medical_specialty In Vitro Techniques Biology Bradykinin Exocytosis Cellular and Molecular Neuroscience chemistry.chemical_compound Catecholamines Developmental Neuroscience Muscarine Internal medicine medicine Animals Secretion Rats Wistar Protein kinase A Phorbol 12 13-Dibutyrate Protein Kinase C Protein kinase C Forskolin Colforsin 3-Pyridinecarboxylic acid 1 4-dihydro-2 6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)- Methyl ester Cyclic AMP-Dependent Protein Kinases Rats Enzyme Activation Perfusion medicine.anatomical_structure Endocrinology Neurology chemistry Adrenal Medulla Chromaffin cell Phorbol Calcium Adrenal medulla Histamine |
| Zdroj: | Neurosignals. 7:307-320 |
| ISSN: | 1424-8638 1424-862X |
| Popis: | Modulatory effects of the activation of either protein kinase C (PKC) by phorbol 12,13-dibutyrate (PDBu) or protein kinase A (PKA) by forskolin on stimulant-evoked secretory processes in the perfused rat adrenal medulla were studied. PDBu or forskolin was applied during repetitive stimulation (30 s each at 10-min intervals) with nicotine, bradykinin, muscarine or histamine, and changes in [Ca2+]i (fura-2 microfluorometry) and catecholamine secretions (electrochemical detection) were simultaneously measured. PDBu markedly potentiated the nicotine-evoked secretion without altering the [Ca2+]i response. PDBu partially inhibited the muscarine-evoked secretion and almost completely blocked the histamine-evoked secretion, concomitantly with extensive suppressions of the [Ca2+]i responses to these stimulants. The bradykinin-evoked secretion was enhanced by PDBu despite a slight attenuation of the [Ca2+]i response. PDBu reduced bradykinin-induced intracellular Ca2+ release in a Ca2+-free medium but enhanced the secretion associated with the released Ca2+. These results suggest that PDBu-activated PKC modulates secretory processes at, at least, two different stages. An early-stage modulation may downregulate receptor/G protein systems, which accounts for the inhibitory effect of PDBu on the muscarine- and histamine-evoked responses. A late-stage modulation may generally promote Ca2+-triggered exocytosis after elevation of [Ca2+]i, which explains the potentiation of the nicotine-evoked secretion by PDBu. The late-stage modulation may counteract the early-stage modulation in bradykinin-stimulated cells. Forskolin potentiated the secretory responses to the four secretagogues without increasing the [Ca2+]i responses. PKA may modulate secretory process at a step(s) distal to the rise in [Ca2+]i as is the case with the late-stage modulation by PKC. |
| Databáze: | OpenAIRE |
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