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OtherCARDIOVASCULAR PHARMACOLOGY

Pharmacological Characterization of the “Silent” 5-Hydroxytryptamine1B-like Receptors of Rabbit Ear Artery

Hassan Movahedi and Ralph E. Purdy
Journal of Pharmacology and Experimental Therapeutics November 1997, 283 (2) 653-660;
Hassan Movahedi
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Ralph E. Purdy
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Abstract

Serotonin acts on 5-hydroxytryptamine (5-HT)1B-likereceptors in isolated rabbit ear artery precontracted with phenylephrine (PHE). These receptors are inactive, or “silent,” in untreated vessels. Ear artery rings were mounted in tissue baths for the measurement of isometric contraction to further characterize these 5-HT1B-like receptors. The 5-HT1-selective receptor agonist sumatriptan failed to contract the untreated ear artery rings but caused a powerful, concentration-dependent contraction in PHE-precontracted vessels. The 5-HT1A/rat 1B receptor antagonist propranolol (1 μM) had no effect, whereas the 5-HT1B receptor antagonists rauwolscine (0.1 μM) and GR127935 (1–100 nM) markedly inhibited the contraction to sumatriptan. In vessels precontracted with phenylephrine, nifedipine reduced and calcium-free medium abolished the contractile response to serotonin. Relaxation to the adenylate cyclase activator forskolin was studied in contracted ear artery rings. Low concentrations (0.1–0.3 μM) of forskolin rapidly and completely relaxed ear artery rings contracted with PHE. In contrast, when PHE-precontracted vessels were contracted with either serotonin or sumatriptan, forskolin caused little or no relaxation at low concentrations and only partial relaxation at 10- to 30-fold higher concentrations. The resistance of these vessels to relaxation by forskolin was markedly reduced in the presence of GR127935 or in ear artery rings from pertussis toxin-treated rabbits. However, pertussis toxin treatment had no effect on the contractile response of PHE-precontracted ear artery rings to serotonin. It is concluded that the silent 5-HT1-like receptor of rabbit ear artery closely resembles the 5-HT1B receptor subtype. This receptor is inversely coupled to adenylate cyclase through a pertussis toxin-sensitive G protein; however, this coupling is unlikely to contribute to the serotonin-induced contraction of PHE-precontracted ear artery rings. Instead, this contraction is mediated at the second-messenger level by pertussis toxin-insensitive influx of calcium.

Footnotes

  • Send reprint requests to: Ralph E. Purdy, Ph.D., Department of Pharmacology, College of Medicine, University of California, Irvine, Irvine, CA 92697-4625.

  • Abbreviations:
    5-HT
    5-hydroxytryptamine
    CRC
    concentration-response curve
    PTX
    pertussis toxin
    PHE
    phenylephrine
    • Received July 29, 1996.
    • Accepted July 17, 1997.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics
Vol. 283, Issue 2
1 Nov 1997
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OtherCARDIOVASCULAR PHARMACOLOGY

Pharmacological Characterization of the “Silent” 5-Hydroxytryptamine1B-like Receptors of Rabbit Ear Artery

Hassan Movahedi and Ralph E. Purdy
Journal of Pharmacology and Experimental Therapeutics November 1, 1997, 283 (2) 653-660;

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OtherCARDIOVASCULAR PHARMACOLOGY

Pharmacological Characterization of the “Silent” 5-Hydroxytryptamine1B-like Receptors of Rabbit Ear Artery

Hassan Movahedi and Ralph E. Purdy
Journal of Pharmacology and Experimental Therapeutics November 1, 1997, 283 (2) 653-660;
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