| Abstract | In [3H]myristic acid-prelabeled Chinese hamster ovary cells stably expressing the rat NK1 tachykinin receptor, the selective NK1 agonist [Pro9]substance P ([Pro9]SP) time and concentration dependently stimulated the formation of [3H]phosphatidylethanol in the presence of ethanol. This [Pro9]SP-induced activation of phospholipase D (PLD) was blocked by NK1 receptor antagonists and poorly or not mimicked by NK2 and NK3 agonists, respectively. In confirmation of previous observations, [Pro9]SP also stimulated the hydrolysis of phosphoinositides, the release of arachidonic acid, and the formation of cyclic AMP (cAMP). All these [Pro9]SP-evoked responses could be mimicked by aluminum fluoride, but they remained unaffected in cells pretreated with pertussis toxin, suggesting that a Gi/Go protein is not involved in these different signaling pathways. The activation of PLD by [Pro9]SP was sensitive to external calcium and required an active protein kinase C because the inhibition of this kinase (Ro 31-8220) or its down-regulation (long-term treatment with a phorbol ester) abolished the response. In contrast, a cAMP-dependent process was not involved in the activation of PLD because the [Pro9]SP-evoked response was neither affected by Rp-8-bromoadenosine 3',5'-cyclic monophosphorothioate nor mimicked by cAMP-generating compounds (cholera toxin or forskolin) or by 8-bromo-cyclic AMP. A functional coupling of NK1 receptors to PLD was also demonstrated in the human astrocytoma cell line U 373 MG stimulated by SP or [Pro9]SP. These results suggest that PLD activation could be an additional signaling pathway involved in the mechanism of action of SP in target cells expressing NK1 receptors. |
| Authors | Y Torrens, J C Beaujouan, M Saffroy, J Glowinski, M Tencé
(Affiliation: Neuropharmacologie, INSERM U114, Collège de France, Paris.)
|
| Journal | Journal of neurochemistry
(J Neurochem)
Vol. 70
Issue 5
Pg. 2091-8
(May 1998)
ISSN: 0022-3042 UNITED STATES |
| PMID | 9572295
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
| Chemical References |
- Glycerophospholipids
- Phosphatidic Acids
- Phosphatidylcholines
- Receptors, Neurokinin-1
- Tachykinins
- phosphatidylethanol
- substance P, Pro(9)-
- Substance P
- Myristic Acid
- Cyclic AMP
- Calcium
- Protein Kinase C
- Phospholipase D
- GTP-Binding Proteins
|
| Topics |
- Animals
- Astrocytoma
(metabolism, pathology)
- CHO Cells
(metabolism)
- Calcium
(pharmacology)
- Cricetinae
- Cyclic AMP
(physiology)
- Enzyme Activation
(drug effects)
- GTP-Binding Proteins
(physiology)
- Glycerophospholipids
- Humans
- Myristic Acid
(metabolism)
- Phosphatidic Acids
(biosynthesis)
- Phosphatidylcholines
(metabolism)
- Phospholipase D
(metabolism)
- Protein Kinase C
(physiology)
- Rats
- Receptors, Neurokinin-1
(metabolism)
- Substance P
(analogs & derivatives, pharmacology)
- Tachykinins
(pharmacology)
- Tumor Cells, Cultured
|
