title: Characterization of sumatriptan-induced contractions in human isolated blood vessels using selective 5-HT(1B) and 5-HT(1D) receptor antagonists and in situ hybridization.
abstract: The 5-HT(1B/1D) receptor agonist sumatriptan is effective in aborting acute attacks of migraine and is known to cause constriction of cranial arteries as well as some peripheral blood vessels. The present study set out to investigate whether 5-HT(1B) and/or 5-HT(1D) receptors mediate contractions of the human isolated middle meningeal and temporal arteries (models for anti-migraine efficacy) and coronary artery and saphenous vein (models for side-effect potential). Concentration-response curves were made with sumatriptan (1 nm-100 microm) in blood vessels in the absence or presence of selective antagonists at 5-HT(1B) (SB224289) and 5-HT(1D) (BRL15572) receptors. SB224289 antagonized sumatriptan-induced contractions in all blood vessels, although the antagonism profile was different amongst these blood vessels. In the temporal artery, SB224289 abolished contraction to sumatriptan, whereas in the middle meningeal artery and saphenous vein sumatriptan-induced contractions were blocked in an insurmountable fashion. Moreover, SB224289 acted as a weak surmountable antagonist in the coronary artery (pK(B): 6.4 +/- 0.2). In contrast, BRL15572 had little or no effect on sumatriptan-induced contractions in the four blood vessels investigated. In situ hybridization revealed the expression of 5-HT(1B) receptor mRNA in the smooth muscle as well as endothelial cells of the blood vessels, whereas the mRNA for the 5-HT(1D) receptor was only very weakly expressed. These results show that the 5-HT(1B) receptor is primarily involved in sumatriptan-induced contractions of human cranial as well as peripheral blood vessels.
authors.affiliation: Department of Pharmacology, Erasmus University Medical Centre Rotterdam, Rotterdam, The Netherlands.
authors.forename: R W M
authors.initials: RW
authors.lastname: van den Broek
authors.forename: P
authors.initials: P
authors.lastname: Bhalla
authors.forename: A Massen
authors.initials: AM
authors.lastname: VanDenBrink
authors.forename: R
authors.initials: R
authors.lastname: de Vries
authors.forename: H S
authors.initials: HS
authors.lastname: Sharma
authors.forename: P R
authors.initials: PR
authors.lastname: Saxena
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D001808:Blood Vessels / Q000187:drug effects* / Q000502:physiology; D001920:Bradykinin / Q000494:pharmacology; D016466:CHO Cells; D002536:Cerebral Arteries / Q000187:drug effects / Q000502:physiology; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology; D006224:Cricetinae; D005260:Female; D006801:Humans; D017403:In Situ Hybridization; D066298:In Vitro Techniques; D008297:Male; D008576:Meningeal Arteries / Q000187:drug effects / Q000502:physiology; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D044302:Receptor, Serotonin, 5-HT1B; D044346:Receptor, Serotonin, 5-HT1D; D011985:Receptors, Serotonin / Q000187:drug effects*; D012501:Saphenous Vein / Q000187:drug effects / Q000502:physiology; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013373:Substance P / Q000494:pharmacology; D018170:Sumatriptan / Q000494:pharmacology*; D014661:Vasoconstriction; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
chemical_list: C470302:HTR1B protein, human; D012333:RNA, Messenger; D044302:Receptor, Serotonin, 5-HT1B; D044346:Receptor, Serotonin, 5-HT1D; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D014662:Vasoconstrictor Agents; D013373:Substance P; D018170:Sumatriptan; D001920:Bradykinin