Tachyphylaxis to the sumatriptan-induced contractile effect in the human uterine artery but not in human cerebral blood vessels: pharmacological demonstration of the 5-HT(1B) receptor functionality loss.
The in vitro contractile response of the human uterine artery to sumatriptan was compared to that of human cerebral blood vessels. Artery rings were prepared for isometric contraction. Tachyphylaxis to the triptan-induced vascular contraction was observed in the uterine artery, but not in basilar and middle cerebral arteries. To evaluate 5-HT(1) receptor subtypes functionality, concentration-response curves to sumatriptan were performed at 0 and 24 h after uterine artery isolation. Both 10 μmol/l cyanopindolol and 63 nmol/l SB 224,289 (5-HT(1B) receptor antagonists) significantly antagonized the contractile response induced by sumatriptan at 0 h but not after 24 h of uterine artery isolation. The 5-HT(1B/1D) receptor antagonist BRL 15,572 at 10 μmol/l significantly antagonized the sumatriptan contractile response at both experimental conditions. We conclude that the tachyphylaxis to sumatriptan observed in the non-cerebral blood vessels, and not in the cerebral ones, may be due to loss of functionality of the 5-HT(1B) receptor subtype, increasing the safety of triptans.
Laboratory of Pharmacology, Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal. sonia@ff.uc.pt
Sónia A
SA
Silva
Carlos A Fontes
CA
Ribeiro
D000328:Adult; D001488:Basilar Artery / Q000187:drug effects / Q000502:physiology*; D001713:Biphenyl Compounds / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D020768:Middle Cerebral Artery / Q000187:drug effects / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D010869:Pindolol / Q000031:analogs & derivatives / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D010881:Piperidones / Q000494:pharmacology; D044302:Receptor, Serotonin, 5-HT1B / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology / Q000502:physiology; D058825:Serotonin 5-HT1 Receptor Agonists / Q000494:pharmacology*; D058829:Serotonin 5-HT1 Receptor Antagonists / Q000494:pharmacology; D013141:Spiro Compounds / Q000494:pharmacology; D018170:Sumatriptan / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D013618:Tachyphylaxis / Q000502:physiology*; D013997:Time Factors; D055988:Uterine Artery / Q000187:drug effects / Q000502:physiology*
D001713:Biphenyl Compounds; D010879:Piperazines; D010881:Piperidones; D044302:Receptor, Serotonin, 5-HT1B; C108518:SB 22489G; D058825:Serotonin 5-HT1 Receptor Agonists; D058829:Serotonin 5-HT1 Receptor Antagonists; D013141:Spiro Compounds; D012701:Serotonin; C047975:cyanopindolol; D018170:Sumatriptan; D010869:Pindolol; C108532:BRL 15572