5-Hydroxytryptamine receptor characterization of human cerebral, middle meningeal and temporal arteries: regional differences.
We have studied the regional distribution of 5-hydroxytryptamine (5-HT) receptor subtypes in fresh circular segments of human cerebral, middle meningeal, and temporal arteries. Vasomotor responses induced by a series of 5-HT agonists and antagonists with some degree of selectivity were studied by using a sensitive in vitro system. Nine 5-HT agonists were examined for contractile effects on the arteries. In cerebral and meningeal arteries 5-carboxamidotryptamine (5-CT) was more potent than 5-HT. The opposite order of potency (5-HT-5-CT) was found in temporal arteries. In the cerebral arteries 5-methoxytryptamine (5-MeOHT) was more potent than sumatriptan while sumatriptan was more potent than 5-MeOHT in meningeal and temporal arteries. The 5-HT1 receptor antagonist, methiothepin, competitively antagonized 5-CT-induced contractions in cerebral arteries, with a pA2 value of 9.05. 5-HT-induced contractions were competitively antagonized by ketanserin (5-HT2) in the temporal arteries pA2 value of 9.06). Methiothepin and ketanserin had non-competitive antagonistic effects in the middle meningeal arteries. The 5-HT3 selective antagonist ondansetron did not cause any shift of the contractions induced by 2-methyl-5-HT in the temporal, cerebral and middle meningeal arteries. These results suggest that the cerebral arteries mainly contain 5-HT1D or 5-HT1-like receptors, and the temporal artery 5-HT2 receptors; the data further indicate the presence of both receptor subtypes in the middle meningeal artery.
Jansen
I
I
Department of Experimental Research, University of Lund, Malmö General Hospital, Sweden.
Olesen
J
J
Edvinsson
L
L
D008735:5-Methoxytryptamine / Q000494:pharmacology; D002536:Cerebral Arteries / Q000737:chemistry* / Q000502:physiology / Q000648:ultrastructure; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D007650:Ketanserin / Q000494:pharmacology; D008576:Meningeal Arteries / Q000737:chemistry* / Q000502:physiology / Q000648:ultrastructure; D008719:Methiothepin / Q000494:pharmacology; D011985:Receptors, Serotonin / Q000032:analysis* / Q000187:drug effects; D012701:Serotonin / Q000031:analogs & derivatives / Q000494:pharmacology; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology; D018170:Sumatriptan; D013699:Temporal Arteries / Q000737:chemistry* / Q000502:physiology / Q000648:ultrastructure; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D007211:Indoles; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D013449:Sulfonamides; D014662:Vasoconstrictor Agents; D012701:Serotonin; D008735:5-Methoxytryptamine; D008719:Methiothepin; D018170:Sumatriptan; C047087:5-carboxamidotryptamine; D007650:Ketanserin