Spinal sumatriptan inhibits capsaicin-induced canine external carotid vasodilatation via 5-HT1B rather than 5-HT1D receptors.
Migraine is a neurovascular disorder associated with trigeminal activation, vasodilatation and trigeminal release of calcitonin gene-related peptide (CGRP). The antimigraine properties of triptans may be due to: i) vasoconstriction of the carotid arterial bed via 5-HT(1B) receptors; and ii) inhibition of CGRP release from trigeminal nerves, via 5-HT(1B/1D) receptors. This study investigated the effects of intrathecally administered sumatriptan (a 5-HT(1B/1D) receptor agonist) and PNU-142633 (a 5-HT(1D) receptor agonist) on the canine external carotid vasodilator responses to capsaicin, alpha-CGRP and acetylcholine. For this purpose, 42 mongrel dogs were anaesthetised with sodium pentobarbitone and, subsequently, vagosympathectomized. The animals were prepared to measure arterial blood pressure, heart rate and external carotid blood flow; the thyroid artery was cannulated for infusion of agonists. 1-min intracarotid (i.c.) continuous infusions of capsaicin, alpha-CGRP and acetylcholine produced dose-dependent increases in external carotid blood flow without affecting arterial blood pressure or heart rate. These vasodilator responses remained unaffected after intrathecal (i.t.) administration of physiological saline (0.5 ml) or PNU-142633 (300-1000 microg); in contrast, i.t. sumatriptan (300-1000 microg) significantly inhibited the vasodilator responses to capsaicin, but not those to alpha-CGRP or acetylcholine. Furthermore, i.t. administration of SB224289 (a 5-HT(1B) receptor antagonist), but not of BRL15572 (a 5-HT(1D) receptor antagonist), abolished the above inhibition by sumatriptan. These results suggest that sumatriptan-induced inhibition of the external carotid vasodilatation to capsaicin involves a central mechanism mainly mediated by 5-HT(1B) receptors.
Muñoz-Islas
Enriqueta
E
Departamento de Farmacobiología, Cinvestav-Coapa, Czda. de los Tenorios 235, Col. Granjas-Coapa, Deleg. Tlalpan, 14330 México D.F., México.
Lozano-Cuenca
Jair
J
González-Hernández
Abimael
A
Ramírez-Rosas
Martha B
MB
Sánchez-López
Araceli
A
Centurión
David
D
Maassenvandenbrink
Antoinette
A
Villalón
Carlos M
CM
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D002211:Capsaicin / Q000494:pharmacology*; D002342:Carotid Artery, External / Q000187:drug effects* / Q000502:physiology; D002839:Chromans / Q000494:pharmacology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006439:Hemodynamics / Q000187:drug effects; D007262:Infusions, Intravenous; D007278:Injections, Spinal; D008297:Male; D010879:Piperazines / Q000494:pharmacology; D010881:Piperidones / Q000494:pharmacology; D044302:Receptor, Serotonin, 5-HT1B / Q000502:physiology*; D044346:Receptor, Serotonin, 5-HT1D / Q000502:physiology*; D058825:Serotonin 5-HT1 Receptor Agonists; D058829:Serotonin 5-HT1 Receptor Antagonists; D013141:Spiro Compounds / Q000494:pharmacology; D018170:Sumatriptan / Q000008:administration & dosage / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
D001713:Biphenyl Compounds; D002839:Chromans; D010879:Piperazines; D010881:Piperidones; D044302:Receptor, Serotonin, 5-HT1B; D044346:Receptor, Serotonin, 5-HT1D; C108518:SB 22489G; D058825:Serotonin 5-HT1 Receptor Agonists; D058829:Serotonin 5-HT1 Receptor Antagonists; D013141:Spiro Compounds; D014662:Vasoconstrictor Agents; D018170:Sumatriptan; D015740:Calcitonin Gene-Related Peptide; C108532:BRL 15572; D000109:Acetylcholine; D002211:Capsaicin; C401885:PNU 142633F