Effect of central serotonin depletion on 5-HT receptor-mediated vasomotor responses in the middle meningeal artery of anaesthetized rats.
1 It has been hypothesized that craniovascular 5-HT receptors mediating dilatation of cranial vessels undergo sensitization on decreased serotonergic transmission in migraine. This study analysed the effect of chemical lesion of the 5-HT system in the brain with 5,7-dihydroxytryptamine (5,7-DHT) on 5-HT receptor-mediated dilator responses to 5-carboxamidotryptamine (5-CT) in the middle meningeal artery of anaesthetized rats. 5-CT has recently been shown to elicit dilator responses in this cranial vessel via 5-HT(7) receptors and, to a much lesser extent, 5-HT(1B/1D) receptors. 2 Pretreatment with 5,7-DHT produced a drastic and selective decrease of 5-HT levels in the brain (78 +/- 6% and 94 +/- 2% in dorsal raphe and hypothalamic paraventricular nuclei, respectively) compared with controls (1% ascorbic acid). 3 Topical application of 5-CT (1-1000 microm) to exposed dura mater encephali produced concentration-dependent decreases in diastolic blood pressure and dilator responses in the middle meningeal artery that were similar in vehicle- and 5,7-DHT-pretreaed animals. 4 Hypotensive and meningeal dilator responses to 5-CT were unaltered by the 5-HT(1B/1D) receptor antagonist, GR-127935 (1 mg kg(-1), i.v.), but were strongly inhibited by the 5-HT(7) receptor antagonist, SB-269970 (1 mg kg(-1), i.v.), with similar efficacy, in both groups of animals. Treatment with GR-127935 + SB-269970 (1 mg kg(-1), i.v. each), produced a stronger inhibitory effect than individual treatments on hypotensive but not on meningeal responses to 5-CT. Meningeal 5-HT(7) receptor-mediated responses (i.e. in GR-127935-pretreated animals) were unchanged by 5,7-DHT pretreatment. 5 Results suggest that the sensitivity of craniovascular 5-HT(7) receptors mediating dilatation is unaffected by a decrease of 5-HT levels in the brain. A neuronal involvement of 5-HT in migraine seems more likely, therefore.
Martínez-García
E
E
Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Zacatenco, Mexico D.F., Mexico.
García-Iglesias
B
B
Terrón
J A
JA
D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology; D000758:Anesthesia; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology; D004298:Dopamine / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D008576:Meningeal Arteries / Q000187:drug effects / Q000502:physiology*; D008578:Meninges / Q000098:blood supply / Q000187:drug effects; D009638:Norepinephrine / Q000378:metabolism; D010069:Oxadiazoles / Q000494:pharmacology; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000378:metabolism; D010636:Phenols / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011903:Raphe Nuclei / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D044302:Receptor, Serotonin, 5-HT1B / Q000502:physiology; D044346:Receptor, Serotonin, 5-HT1D / Q000502:physiology; D011985:Receptors, Serotonin / Q000502:physiology*; D012701:Serotonin / Q000031:analogs & derivatives / Q000172:deficiency* / Q000378:metabolism / Q000494:pharmacology; D058829:Serotonin 5-HT1 Receptor Antagonists; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
D010069:Oxadiazoles; D010636:Phenols; D010879:Piperazines; D044302:Receptor, Serotonin, 5-HT1B; D044346:Receptor, Serotonin, 5-HT1D; D011985:Receptors, Serotonin; C404922:SB 269970; D058829:Serotonin 5-HT1 Receptor Antagonists; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D013449:Sulfonamides; C104425:serotonin 7 receptor; C090701:GR 127935; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; C047087:5-carboxamidotryptamine; D004298:Dopamine; D009638:Norepinephrine