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

• Published in: British journal of pharmacology 2002-05, Vol.136 (2), p.171-176
• Main Authors: Akin, Demet, Onaran, H Ongun, Gurdal, Hakan
• Format: Article
• Language: English
• Subjects: 5‐HT1B receptors; 5‐HT1D receptors; adenylate cyclase inhibition; Animals; Biological and medical sciences; Carotid Artery, Common - drug effects; Carotid Artery, Common - metabolism; cyclic AMP; Cyclic AMP - antagonists & inhibitors; Cyclic AMP - metabolism; Dose-Response Relationship, Drug; In Vitro Techniques; Indoles - pharmacology; Medical sciences; naratriptan; Neuropharmacology; Neurotransmitters. Neurotransmission. Receptors; Pharmacology. Drug treatments; Piperidines - pharmacology; Protein Transport - drug effects; Protein Transport - physiology; rabbit common carotid artery; Rabbits; Serotonin Receptor Agonists - pharmacology; Serotoninergic system; Sumatriptan; Sumatriptan - pharmacology; Tryptamines; vascular contractions; Vasoconstriction - drug effects; Vasoconstriction - physiology
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1038/sj.bjp.0704710

Sumatriptan or eletriptan produced vasocontraction in common carotid artery (CCA) by stimulating 5HT1B receptors (see also Akin & Gurdal, this issue). Naratriptan as a 5HT1B/D agonist, was unable to produce vasocontraction in this artery, but inhibited the vasocontractile response induced by sumatriptan or eletriptan. All these agonists inhibited forskolin‐stimulated cyclic AMP production with comparable potencies and maximal responses. This inhibition was mediated by 5HT1B receptors: 5HT1B antagonist SB216641 (1 μM) completeley antagonized sumatriptan‐, eletriptan‐ or naratriptan‐induced cyclic AMP inhibition, but 5HT1D antagonist BRL15572 (1 μM) did not affect this response. Naratriptan‐induced stimulation of 5‐HT1B 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 5HT1B‐mediated inhibition of adenylate cyclase was not a sufficient condition to couple the receptor stimulation to vasocontraction. We discussed agonist‐induced trafficking as a plausible mechanism for the observed phenomenon. British Journal of Pharmacology (2002) 136, 171–176; doi:10.1038/sj.bjp.0704710