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

Abstract

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-HT₁ 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.

Validation of canine uterine and testicular arteries for the functional characterisation of receptor-mediated contraction as a replacement for laboratory animal tissues in teaching

“…These results may suggest that canine uterine tissue might exhibit desensitisation of 5-HT receptors as a result of the presence of oestrogen pre-neutering causing a prolonged exposure to 5-HT [13]. One human study evaluating uterine artery contractility to sumatriptan, a 5-HT 1 receptor agonist [28], showed that tachyphylaxis occurred in uterine arteries and also showed that this does not occur with cerebral arteries [28].…”