Cholinergic-induced [3H] noradrenaline release in rat brain cortical slices is mediated via a pertussis toxin sensitive GTP binding protein and involves activation of protein kinase C
| Autor: | Itzhak Lev Ari, Lydia Schwarz, Daphine Atlas |
|---|---|
| Rok vydání: | 1989 |
| Předmět: |
Male
Cholera Toxin G protein Carbazoles Biology In Vitro Techniques Pertussis toxin medicine.disease_cause Piperazines Indole Alkaloids Potassium Chloride chemistry.chemical_compound Norepinephrine Phenylephrine GTP-Binding Proteins 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine medicine Animals Virulence Factors Bordetella Ouabain Protein kinase C Protein Kinase C Diacylglycerol kinase Polymyxin B Cerebral Cortex Veratridine Phospholipase C Neurosecretion Cholera toxin Cell Biology Isoquinolines Molecular biology Acetylcholine Rats chemistry Pertussis Toxin Carbachol K252a |
| Zdroj: | Cellular signalling. 1(5) |
| ISSN: | 0898-6568 |
| Popis: | The involvement of a GTP-binding protein (G-protein) in the process of neurotransmitter release was examined using pertussis toxin and cholera toxin. Cholinergic agonists are shown to mediate [3H]noradrenaline release in rat brain slices via a pertussis toxin (1.2 micrograms/ml) sensitive, and cholera toxin (0.5 microgram/ml) insensitive G-protein. An indication for the involvement of a G-protein and phospholipase C activation in the release process was implied from the inhibitory effect of neomycin on K+-, veratridine- and carbachol-induced-norepinephrine release. Depolarizing agents mediate a neomycin-sensitive release, which is not which is not affected either by pertussis toxin or cholera toxin, suggesting a different mode of phospholipase C activation, unlike carbachol-induced release, which is both neomycin and pertussis toxin sensitive. Similarly, a hormone-sensitive carrier activated by phenylephrine not via alpha 1-adrenergic receptors, mediates a non-exocytosis efflux which is not affected by neomycin and is shown to be pertussis toxin-insensitive. The inhibitory action of protein kinase C inhibitors polymyxin B, K252a and H-7 [(1-(5-isoquinolinesulphonyl)-2-methyl-piperazine] on release, strongly suggests its participation in the process. Polymyxin B, a relatively selective protein kinase C inhibitor, inhibited carbachol-induced release (IC50 = 0.53 microM) as well as the K+ and the veratridine induced [3H] noradrenaline release, K252a, an inhibitor of various protein kinases at the ATP site, and H-7, another protein kinase C inhibitor, inhibited carbachol-induced noradrenaline released with IC50 = 35 nM and 3 microM respectively. Consistent with its inability to activate phospholipase C, phenylephrine-induced noradrenaline efflux was unaffected by polymyxin B (greater than 70 microM). These results offer more supportive evidence for a major role played by the dual messengers inositol trisphosphate and diacylglycerol (IP3/DG) in the mechanisms of neuronal release. |
| Databáze: | OpenAIRE |
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