5-HT1B receptors and alpha 2A/2C-adrenoceptors mediate external carotid vasoconstriction to dihydroergotamine.
Dihydroergotamine produces external carotid vasoconstriction in vagosympathectomized dogs by 5-HT(1B/1D) receptors and alpha(2)-adrenoceptors. This study identified the specific subtypes involved in this response. One-minute intracarotid infusions of dihydroergotamine (5.6-10 microg/min) dose-dependently decreased external carotid blood flow without affecting blood pressure or heart rate. This response was: (1) partly blocked in dogs pretreated intravenously with the antagonists SB224289 (5-HT(1B); 2,3,6,7-tetrahydro-1'-methyl-5-[2'-methyl-4' (5-methyl-1,2,4-oxadiazol-3-yl)biphenyl-4-carbonyl]furo[2,3-f]indole-3-spiro-4'-piperidine hydrochloride), rauwolscine (alpha(2)), BRL44408 (alpha(2A); 2-[2H-(1-methyl-1,3-dihydroisoindole)methyl]-4,5-dihydroimidazole) or MK912 (alpha(2C); (2S,12bS)-1'3'-dimethylspiro(1,3,4,5',6,6',7,12b-octahydro-2Hbenzo[b]furo[2,3-a]quinazoline)-2,4'-pyrimidin-2'-one); (2) markedly blocked after SB224289 plus rauwolscine; and (3) unaffected after BRL15572 (5-HT(1D); 1-(3-chlorophenyl)-4-[3,3-diphenyl (2-(S,R) hydroxypropanyl) piperazine] hydrochloride) or imiloxan (alpha(2B)). Therefore, the above response involves 5-HT(1B) receptors and alpha(2A/2C)-adrenoceptors.
Villalón
Carlos M
CM
Departamento de Farmacobiología, CINVESTAV-IPN, Calzada de los Tenorios 235, Col. Granjas Coapa, Deleg. Tlalpan, C.P. 14330 México, D.F., Mexico. carlos_villalon@infosel.net.mx
Centurión
David
D
Willems
Edwin W
EW
Arulmani
Udayasankar
U
Saxena
Pramod R
PR
Valdivia
Luis F
LF
D018674:Adrenergic Antagonists / Q000494:pharmacology; D058669:Adrenergic alpha-2 Receptor Antagonists; D000818:Animals; D002342:Carotid Artery, External / Q000187:drug effects / Q000502:physiology*; D004087:Dihydroergotamine / Q000494:pharmacology*; D004285:Dogs; D008297:Male; D044302:Receptor, Serotonin, 5-HT1B / Q000502:physiology*; D018341:Receptors, Adrenergic, alpha-2 / Q000502:physiology*; D058829:Serotonin 5-HT1 Receptor Antagonists; D012702:Serotonin Antagonists / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*
D018674:Adrenergic Antagonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D044302:Receptor, Serotonin, 5-HT1B; D018341:Receptors, Adrenergic, alpha-2; D058829:Serotonin 5-HT1 Receptor Antagonists; D012702:Serotonin Antagonists; D004087:Dihydroergotamine