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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Adams, D. Garland, C. J. Hinton, J. M. |
| Description | Author Affiliation: Hinton JM ( Department of Pharmacology, School of Medical Sciences, University of Bristol.) |
| Abstract | 1. The involvement of phospholipase D (PLD) in the 5-hydroxytryptamine 5-HT1B/5-HT1D-signalling pathway was assessed in the rabbit isolated mesenteric artery. 2. RT-PCR analysis of mesenteric smooth muscle cells revealed a strong signal corresponding to mRNA transcript for the 5-HT1B receptor. The PCR fragment corresponded to the known sequence for the 5-HT1B receptor. No signal corresponding to 5-HT1D mRNA was detected. 3. Neither 5-HT (3 microM) nor KCl (45 mM) individually stimulated any significant increase in the smooth muscle concentration of [33P]-PtdBut to reflect PLD activity. However, in the presence of KCl (45 mM), 5-HT evoked a concentration-dependent increase in [33P]-PtdBut, to a maximum of 84% with 5-HT (3 microM). 4. [33P]-PtdBut accumulation evoked by 5-HT in the presence of KCl was abolished in nominally calcium-free Krebs-Henseleit Buffer (KHB) or with the selective protein kinase C inhibitor, Ro-31 8220 (10 microM, 20 min). 5. 5-HT (3 microM) in the presence of KCl (45 mM) failed to increase either the accumulation of [33P]-phosphatidic acid in the presence of butanol, or total [3H]-inositol phosphates ([3H]-InsP) in the presence of LiCl (10 mM). 6. 5-HT (0.1-1 microM) abolished forskolin (1 microM) stimulated increases in cyclic AMP (15 fold increase), an action which was pertussis toxin-sensitive. 7. Therefore, in the presence of raised extracellular potassium 5-HT can stimulate PLD via 5-HT1B receptors in the rabbit mesenteric artery. This action requires extracellular calcium and the activation of protein kinase C. These characteristics are identical to the profile for 5-HT1B/5-HT1D-receptor evoked contraction in vascular smooth muscle cells, suggesting a role for PLD in this response to 5-HT. |
| ISSN | 00071188 |
| e-ISSN | 14765381 |
| Journal | British Journal of Pharmacology |
| Issue Number | 7 |
| Volume Number | 126 |
| Language | English |
| Publisher | Wiley Online Library(on behalf of The British Pharmacological Society) |
| Publisher Date | 1999-04-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | Open |
| Subject Keyword | Mesenteric Arteries Enzymology Phospholipase D Physiology Serotonin Pharmacology Animals Cyclic AMP Glycerophospholipids Metabolism In Vitro Techniques Indoles Pertussis Toxin Protein Kinase C Rabbits Receptor, Serotonin, 5-HT1B Receptor, Serotonin, 5-HT1D Receptors, Serotonin Reverse Transcriptase Polymerase Chain Reaction Vasoconstriction Drug Effects Virulence Factors, Bordetella Research Support, Non-U.S. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology |
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