Effects of chronic sumatriptan and zolmitriptan treatment on 5-HT receptor expression and function in rats.
Triptans are commonly used anti-migraine drugs and show agonist action mainly at serotonin 5-HT(1B/1D/1F) receptors. It is not known whether frequent or long-term treatment with these drugs would alter 5-HT receptor function. We investigated the effects of protracted (14-18 days) sumatriptan and zolmitriptan treatment in rats on 5-HT(1) receptor mRNA expression and function in tissues related to migraine pathophysiology. RT-PCR analysis revealed that 5-HT(1B/1D/1F) receptor mRNA was reduced in the trigeminal ganglion after treatment with either triptan (reduction by: sumatriptan 39% and zolmitriptan 61% for 5-HT(1B); 60%vs 41% for 5-HT(1D); 32%vs 68% for 5-HT(1F)). Sumatriptan attenuated 5-HT(1D) receptor mRNA by 49% in the basilar artery, whereas zolmitriptan reduced 5-HT(1B) mRNA in this tissue by 70%. No change in 5-HT(1) receptor mRNA expression was observed in coronary artery and dura mater. Chronic triptan treatment had no effect in two functional assays [sumatriptan mediated inhibition (50 mg/kg, i.p.) of electrically induced plasma protein extravasation in dura mater and 5-nonyloxytryptamine-stimulated [(35)S]guanosine-5'-O-(3-thio)triphosphate binding in substantia nigra]. Furthermore, vasoconstriction to 5-HT in isolated basilar artery was not affected by chronic triptan treatment, while it was slightly reduced in coronary artery. We conclude that, although our treatment protocol altered mRNA receptor expression in several tissues relevant to migraine pathophysiology, it did not attenuate 5-HT(1) receptor-dependent functions in rats.
Reuter
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U
Stroke and Neurovascular Regulation Laboratory, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA. uwe.reuter@charite.de
Salomone
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Ickenstein
G W
GW
Waeber
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C
D000818:Animals; D001345:Autoradiography; D001488:Basilar Artery / Q000187:drug effects / Q000378:metabolism; D003331:Coronary Vessels / Q000187:drug effects / Q000378:metabolism; D004388:Dura Mater / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009924:Organ Culture Techniques; D023303:Oxazolidinones / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D044263:Receptors, Serotonin, 5-HT1 / Q000187:drug effects*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D018170:Sumatriptan / Q000494:pharmacology*; D013997:Time Factors; D012668:Trigeminal Ganglion / Q000187:drug effects / Q000378:metabolism; D014363:Tryptamines; D014661:Vasoconstriction / Q000187:drug effects
D023303:Oxazolidinones; D012333:RNA, Messenger; D044263:Receptors, Serotonin, 5-HT1; D017366:Serotonin Receptor Agonists; D014363:Tryptamines; C089750:zolmitriptan; D018170:Sumatriptan