Involvement of 5-HT1B receptors in collar-induced hypersensitivity to 5-hydroxytryptamine of the rabbit carotid artery

Br J Pharmacol. 1999 Jul;127(6):1327-36. doi: 10.1038/sj.bjp.0702684.

Abstract

In humans intimal thickening is aprerequisite of atherosclerosis. Application of a silicone collar around the rabbit carotid artery induces an intimal thickening but in addition it increases the sensitivity to the vasoconstrictor action of serotonin (5-hydroxytryptamine, 5-HT). The 5-HT receptors involved in collar-induced hypersensitivity to 5-HT were investigated using several agonists and antagonists. One week after placement of collars around both carotid arteries of anaesthetized rabbits, rings (2 mm width) from inside (=collar) and outside (=sham) the collars were mounted in organ baths (10 ml) for isometric force measurements at 6 g loading tension. Collared rings were more sensitive to the contractile effect of 5-HT (7.6 fold) and 5-carboxamidotryptamine (31 fold, 5-CT, 5-HT1 agonist) in cumulative concentration response curves. Sumatriptan (5-HT1B/1D agonist) caused concentration-dependent constrictions in collared rings only. Collar placement did not significantly alter pA2 values (Schild regression) or apparent pKb values (non-linear regression) of spiperone and methysergide (mixed 5-HT2A/5-HT1 antagonists) or ketanserin and ritanserin (5-HT2A antagonists), indicating unchanged binding characteristics of the 5-HT2A receptor. However, the reduced slope of the Schild regression pointed to a heterogeneous receptor population in collared rings. In contrast, the apparent pKb value of methiothepin (5-HT1B antagonist) was significantly reduced by collar placement, and its antagonism shifted from non-surmountable in sham rings to surmountable in collared segments. Taken together, this study demonstrates that the serotonergic receptor involved in the hypersensitivity to 5-HT of rabbit collared carotid artery is a 5-HT1B receptor subtype.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 8-Hydroxy-2-(di-n-propylamino)tetralin / pharmacology
  • Animals
  • Braces / adverse effects*
  • Carotid Arteries / drug effects*
  • Carotid Arteries / physiopathology
  • Dose-Response Relationship, Drug
  • Hypersensitivity / etiology*
  • In Vitro Techniques
  • Ketanserin / pharmacology
  • Male
  • Methysergide / pharmacology
  • Oxadiazoles / pharmacology
  • Piperazines / pharmacology
  • Potassium Chloride / pharmacology
  • Rabbits
  • Receptor, Serotonin, 5-HT1B
  • Receptor, Serotonin, 5-HT2A
  • Receptors, Serotonin / drug effects
  • Receptors, Serotonin / physiology*
  • Ritanserin / pharmacology
  • Serotonin / analogs & derivatives
  • Serotonin / pharmacology*
  • Serotonin Antagonists / pharmacology
  • Serotonin Receptor Agonists / pharmacology
  • Spiperone / pharmacology
  • Sumatriptan / pharmacology
  • Tryptamines / pharmacology
  • Vasoconstriction / drug effects

Substances

  • Oxadiazoles
  • Piperazines
  • Receptor, Serotonin, 5-HT1B
  • Receptor, Serotonin, 5-HT2A
  • Receptors, Serotonin
  • Serotonin Antagonists
  • Serotonin Receptor Agonists
  • Tryptamines
  • 1-(2-methoxyphenyl)-4-(4-(2-phthalimido)butyl)piperazine
  • L 694247
  • Ritanserin
  • Serotonin
  • Spiperone
  • Potassium Chloride
  • 8-Hydroxy-2-(di-n-propylamino)tetralin
  • Sumatriptan
  • 5-carboxamidotryptamine
  • Ketanserin
  • Methysergide