5-HT1B receptors, alpha2A/2C- and, to a lesser extent, alpha1-adrenoceptors mediate the external carotid vasoconstriction to ergotamine in vagosympathectomised dogs.
It has previously been suggested that ergotamine produces external carotid vasoconstriction in vagosympathectomised dogs via 5-HT1B/1D receptors and alpha2-adrenoceptors. The present study has reanalysed this suggestion by using more selective antagonists alone and in combination. Fifty-two anaesthetised dogs were prepared for ultrasonic measurements of external carotid blood flow. The animals were divided into thirteen groups (n=4 each) receiving an i.v. bolus injection of, either physiological saline (0.3 ml/kg; control), or the antagonists SB224289 (300 microg/kg; 5-HT1B), BRL15572 (300 microg/kg; 5-HT1D), rauwolscine (300 microg/kg; alpha2), SB224289 + BRL15572 (300 microg/kg each), SB224289 + rauwolscine (300 microg/kg each), BRL15572 + rauwolscine (300 microg/kg each), rauwolscine (300 microg/kg) + prazosin (100 microg/kg; alpha1), SB224289 (300 microg/kg) + prazosin (100 microg/kg), SB224289 (300 microg/kg) + rauwolscine (300 microg/kg) + prazosin (100 microg/kg), SB224289 (300 microg/kg) + prazosin (100 microg/kg) + BRL44408 (1,000 microg/kg; alpha2A), SB224289 (300 microg/kg) + prazosin (100 microg/kg)+ imiloxan (1,000 microg/kg; alpha2B), or SB224289 (300 microg/kg) + prazosin (100 microg/kg) + MK912 (300 microg/kg; alpha2C). Each group received consecutive 1-min intracarotid infusions of ergotamine (0.56, 1, 1.8, 3.1, 5.6, 10 and 18 microg/min), following a cumulative schedule. In saline-pretreated animals, ergotamine induced dose-dependent decreases in external carotid blood flow without affecting arterial blood pressure or heart rate. These control responses were: unaffected by SB224289, BRL15572, rauwolscine or the combinations of SB224289 + BRL15572, BRL15572 + rauwolscine, rauwolscine + prazosin, SB224289 + prazosin, or SB224289 + prazosin + imiloxan; slightly blocked by SB224289 + rauwolscine; and markedly blocked by SB224289 + rauwolscine + prazosin, SB224289 + prazosin + BRL44408 or SB224289 + prazosin + MK912. Thus, the cranio-selective vasoconstriction elicited by ergotamine in dogs is predominantly mediated by 5-HT1B receptors as well as alpha2A/2C-adrenoceptor subtypes and, to a lesser extent, by alpha1-adrenoceptors.
Valdivia
Luis F
LF
Departamento de Farmacobiología, CINVESTAV-IPN, Czda. de los Tenorios 235, Col. Granjas Coapa, Deleg. Tlalpan, CP 14330, México DF, México.
Centurión
David
D
Arulmani
Udayasankar
U
Saxena
Pramod R
PR
Villalón
Carlos M
CM
D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002342:Carotid Artery, External / Q000187:drug effects*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D004878:Ergotamine / Q000494:pharmacology*; D007022:Hypotension / Q000139:chemically induced; D007093:Imidazoles / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D007275:Injections, Intravenous; D054833:Isoindoles; D008297:Male; D010879:Piperazines / Q000494:pharmacology; D010881:Piperidones / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011807:Quinolizines / Q000494:pharmacology; D044302:Receptor, Serotonin, 5-HT1B / Q000187:drug effects / Q000502:physiology*; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D013141:Spiro Compounds / Q000494:pharmacology; D013562:Sympathectomy / Q000379:methods; D014628:Vagotomy / Q000379:methods; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D015016:Yohimbine / Q000494:pharmacology
D001713:Biphenyl Compounds; D007093:Imidazoles; D007211:Indoles; D054833:Isoindoles; D010879:Piperazines; D010881:Piperidones; D011807:Quinolizines; D044302:Receptor, Serotonin, 5-HT1B; D011942:Receptors, Adrenergic, alpha; C108518:SB 22489G; D013141:Spiro Compounds; C054290:L 657743; D015016:Yohimbine; C108532:BRL 15572; D004878:Ergotamine; D011224:Prazosin; C072125:BRL 44408; C044484:Imiloxan