2-(2-Aminoethyl)-quinoline (D-1997): a novel agonist at 5-hydroxytryptamine1-like receptors in the canine basilar artery.
This study aimed to investigate the mechanisms involved in the contractile effects produced by the novel quinoline derivative, 2-(2-aminoethyl)-quinoline (D-1997), in the canine isolated basilar artery. For comparison, the effects of D-1997 were also evaluated on rat aorta. Canine basilar artery and rat aortic rings were prepared and mounted in organ baths to record isometric tension changes. The contractile effects of D-1997 in the basilar artery were compared with those produced by 5-hydroxytryptamine (5-HT) and the 5-HT receptor agonist quipazine. Thus, 4-HT (10(-10)-10(-6)M), D-1997 (3.1 x 10(-8)-10(-4) M) and quipazine (3.1 x 10(-7)-10(-4) M) each caused concentration-dependent contractions of the canine basilar artery with a rank order of agonist potency of 5-HT > D-1997 > quipazine. 5-HT and D-1997 exhibited similar maximum effects which were higher than that of quipazine. Similar concentrations of D-1997 failed to produce contraction in rat aorta. The effects of D-1997 in the basilar artery were not modified by incubation with either the 5-HT2 receptor antagonist ketanserin (0.01-1 microM), the 5-HT3 and 5-HT4 receptor antagonist ICS205930 (tropisetron; 0.1-10 microM), the 5-HT1A receptor antagonist spiroxatrine (0.01-1 microM), the beta-adrenoceptor blocker with high affinity for 5-HT1A and 5-HT1B binding sites (+/-)-pindolol (0.01-1 microM), or the alpha 1-adrenoceptor antagonist prazosin (0.01-1 microM). In contrast, the D-1997-induced responses were potently and concentration-dependently antagonized by the mixed 5-HT1-like and 5-HT2 receptor antagonist methiothepin (0.01-1 microM). It is concluded that D-1997 contracts the canine basilar artery by stimulating 5-HT1-like receptors unrelated to either the 5-HT1A or 5-HT1B receptor subtypes. The compound seems to be devoid of 5-HT2 receptor agonist properties in rat aorta.
Terrón
J A
JA
Departamento de Farmacología y Toxicologia, CINVESTAV, Instituto Politécnico Nacional, México, D.F., México.
López-Muñoz
F J
FJ
Hong
E
E
Villalón
C M
CM
D000818:Animals; D001488:Basilar Artery / Q000187:drug effects* / Q000502:physiology; D004146:Dioxanes / Q000494:pharmacology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D008719:Methiothepin / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology*; D011814:Quipazine / Q000494:pharmacology; D051381:Rats; D012701:Serotonin / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013141:Spiro Compounds / Q000494:pharmacology; D000077526:Tropisetron; D014661:Vasoconstriction / Q000187:drug effects*
C089626:2-(2-aminoethyl)quinoline hydrochloride; D004146:Dioxanes; D007211:Indoles; D011804:Quinolines; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D013141:Spiro Compounds; D012701:Serotonin; D011814:Quipazine; D008719:Methiothepin; D000077526:Tropisetron; D007650:Ketanserin; C018387:spiroxatrine