An endothelial 5-HT receptor that mediates relaxation in guinea-pig isolated jugular vein resembles the 5-HT1D subtype.
1. Endothelium-dependent and -independent, concentration-related, relaxations to 5-hydroxytryptamine (5-HT) are described in a preparation of guinea-pig isolated jugular vein. 2. An endothelial 5-HT receptor was studied in the presence of mesulergine (at 10.0 microM, a concentration sufficient to antagonize 5-HT2 receptor-mediated contractions and endothelium-independent relaxations to 5-HT). Relaxations mediated by the endothelial 5-HT receptor were resistant to antagonism by mesulergine. 3. Several 5-HT receptor agonists activated the endothelial receptor with the following rank order of potency: 5-carboxamidotryptamine (5-CT) greater than 5-HT greater than methysergide greater than or equal to alpha-methyl-5-HT greater than sumatriptan greater than 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) greater than 2-methyl-5-HT. 4. Relaxations to 5-HT were not blocked by (+/-)-pindolol (1.0 microM), (-)-propranolol (1.0 microM), spiperone (1.0 microM), ondansetron (1.0 microM) or ICS 205-930 (10.0 microM). 5. Both 5-HT and sumatriptan evoked endothelium-dependent relaxations which were sensitive to antagonism (pA2 and apparent pA2 values respectively) by methiothepin (8.1 and 8.6), metergoline (7.4 and 7.5), PAPP (8.2 and 8.2), yohimbine (7.1 and 6.8), rauwolscine (6.8 and 6.7), but not by corynanthine (10.0 microM). 6. These observations are consistent with a 5-HT1D receptor-mediated effect, and provide further support for the concept that differences exist between endothelial 5-HT receptors in different tissues and species.
Gupta
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Department of Biomedical Research, Wyeth Research (UK) Ltd., Maidenhead, Berkshire.
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D004730:Endothelium, Vascular / Q000502:physiology*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007601:Jugular Veins / Q000187:drug effects / Q000502:physiology*; D008297:Male; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011985:Receptors, Serotonin / Q000032:analysis / Q000187:drug effects / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
D011450:Prostaglandin Endoperoxides, Synthetic; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D014662:Vasoconstrictor Agents; D012701:Serotonin; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid