Unravelling the pharmacological profile of the canine external carotid vasodilator '5-HT1-like' receptors: coexistence of sympatho-inhibitory 5-HT1B and postjunctional 5-HT7 receptors.
It has been suggested that the external carotid vasodilatation produced by serotonin (5-hydroxytryptamine; 5-HT) in anaesthetised dogs with intact vagosympathetic trunks is mediated by sympatho-inhibitory '5-HT1D' receptors and musculotropic '5-HT1-like' receptors. The present study has re-analysed this suggestion with regard to the classification schemes recently proposed by the NC-IUPHAR subcommittee on 5-HT receptors. In pentobarbital-anaesthetised dogs with intact vagosympathetic trunks, 1-min intracarotid (i.c.) infusions of 5-carboxamidotryptamine (5-CT; 0.01-0.3 microg/min), 5-HT (0.3-30 microg/ min), 5-methoxytryptamine (5-MeO-T; 1-100 microg/min) or sumatriptan (1-100 microg/min) dose-dependently increased the external carotid blood flow without affecting blood pressure or heart rate. The selective 5-HT1D receptor agonist, PNU-142633 (1-1000 microg/min), was essentially inactive. After mesulergine (300 microg/kg, i.v.), an antagonist at cardiovascular 5-HT7 receptors, the above responses to 5-HT, 5-CT and 5-MeO-T were blocked, whilst those to sumatriptan remained unaffected. In contrast, after the 5-HT1B/1D receptor antagonist, GR127935 (10 microg/kg, i.v.), the responses to 5-HT, 5-CT and 5-MeO-T were not affected, but those to sumatriptan were abolished. Furthermore, after the selective 5-HT1B receptor antagonist, SB224289 (300 microg/kg, i.v.), the responses to 5-HT, 5-CT and 5-MeO-T were significantly enhanced, whereas those to sumatriptan were abolished. Interestingly, the responses to all these agonists remained unmodified after the selective 5-HT1D receptor antagonist, BRL15572 (300 microg/kg, i.v.). The above results suggest that the '5-HT1-like' receptors, which mediate canine external carotid vasodilatation, display the pharmacological profile of sympatho-inhibitory 5-HT1B receptors and musculotropic 5-HT7 receptors, and confirm the existence of vasoconstrictor 5-HT1B receptors.
Villalón
C M
CM
Departamento de Farmacobiología, CINVESTAV-IPN, México. carlos_villalon@infosel.net.mx
Sánchez-López
A
A
Centurión
D
D
Saxena
P R
PR
D008735:5-Methoxytryptamine / Q000494:pharmacology; D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology; D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002342:Carotid Artery, External / Q000187:drug effects / Q000502:physiology*; D002839:Chromans / Q000494:pharmacology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D009469:Neuromuscular Junction / Q000502:physiology; D010069:Oxadiazoles / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D010881:Piperidones / Q000494:pharmacology; D044302:Receptor, Serotonin, 5-HT1B; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D044263:Receptors, Serotonin, 5-HT1; D012701:Serotonin / Q000031:analogs & derivatives* / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013141:Spiro Compounds / Q000494:pharmacology; D018170:Sumatriptan / Q000494:pharmacology; D013564:Sympathetic Nervous System / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
D001713:Biphenyl Compounds; D002839:Chromans; D010069:Oxadiazoles; D010879:Piperazines; D010881:Piperidones; D044302:Receptor, Serotonin, 5-HT1B; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; C108518:SB 22489G; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D013141:Spiro Compounds; C104425:serotonin 7 receptor; C090701:GR 127935; D012701:Serotonin; D008735:5-Methoxytryptamine; D018170:Sumatriptan; C047087:5-carboxamidotryptamine; C108532:BRL 15572; D000109:Acetylcholine; C401885:PNU 142633F