Agonist-directed trafficking explaining the difference between response pattern of naratriptan and sumatriptan in rabbit common carotid artery

Br J Pharmacol. 2002 May;136(2):171-6. doi: 10.1038/sj.bjp.0704710.

Abstract

1. Sumatriptan or eletriptan produced vasocontraction in common carotid artery (CCA) by stimulating 5HT(1B) receptors (see also Akin & Gurdal, this issue). 2. Naratriptan as a 5HT(1B/D) agonist, was unable to produce vasocontraction in this artery, but inhibited the vasocontractile response induced by sumatriptan or eletriptan. 3. All these agonists inhibited forskolin-stimulated cyclic AMP production with comparable potencies and maximal responses. This inhibition was mediated by 5HT(1B) receptors: 5HT(1B) antagonist SB216641 (1 microM) completeley antagonized sumatriptan-, eletriptan- or naratriptan-induced cyclic AMP inhibition, but 5HT(1D) antagonist BRL15572 (1 microM) did not affect this response. 4. Naratriptan-induced stimulation of 5-HT(1B) receptors resulted only in adenylate cyclase inhibition, whereas stimulation of these receptors by sumatriptan or eletriptan produced vasocontraction as well. Hence, we concluded that the 5HT(1B)-mediated inhibition of adenylate cyclase was not a sufficient condition to couple the receptor stimulation to vasocontraction. 5. We discussed agonist-induced trafficking as a plausible mechanism for the observed phenomenon.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carotid Artery, Common / drug effects*
  • Carotid Artery, Common / metabolism
  • Cyclic AMP / antagonists & inhibitors
  • Cyclic AMP / metabolism
  • Dose-Response Relationship, Drug
  • In Vitro Techniques
  • Indoles / pharmacology*
  • Piperidines / pharmacology*
  • Protein Transport / drug effects
  • Protein Transport / physiology
  • Rabbits
  • Serotonin Receptor Agonists / pharmacology*
  • Sumatriptan / pharmacology*
  • Tryptamines
  • Vasoconstriction / drug effects*
  • Vasoconstriction / physiology

Substances

  • Indoles
  • Piperidines
  • Serotonin Receptor Agonists
  • Tryptamines
  • Sumatriptan
  • Cyclic AMP
  • naratriptan