5-HT1-LIKE AND 5-HT2A RECEPTORS MEDIATE 5-HYDROXYTRYPTAMINE-INDUCED CONTRACTION OF RABBIT ISOLATED MESENTERIC-ARTERY

The contractions induced by 5-hydroxytryptamine (5-HT) and the 5-HT1-like receptor agonist, sumatriptan, were investigated in the open ring preparations of rabbit mesenteric artery in order to characterize the 5-HT receptors. 5-HT induced concentration-dependent contractions. Sumatriptan did not induce any contraction of unstimulated rings, whereas it elicited concentration-dependent contractions in preparations given a moderate tone by a threshold concentration of prostaglandin F-2 alpha (PGF(2 alpha)). Pargyline, cocaine or normetanephrine were without significant effect on the contractions induced by 5-HT and sumatripan. The 5-HT concentration-effect curve was clearly biphasic. Methiothepin (0.01 mu M) shifted the both phases of the concentration-effect curve to the right. Ketanserin (0.1 mu M) Shifted the second, low affinity, phase and prazosin did not alter concentration-effect curve to 5-HT. The sumatriptan concentration-effect curve was shifted by methiothepin (0.01 mu M) to the right (pK(B) = 9.19) but not by ketanserin (1 mu M). Concentration-effect curves to 5-HT and sumatriptan were not affected by the 5-HT3 receptor antagonist tropisetron (1 mu M) These results suggest that 5-HT1-like type receptors are responsible for the first phase of 5-HT-induced contraction and 5-HT2A receptor for the second phase, in rabbit mesenteric artery. Sumatriptan-induced contractions appear to be mediated by 5-HT1-like type receptors in this artery. These results also suggest that this kind of amplification may be a common feature of vascular 5-HT1-like type receptor as has been shown in other vascular segments such as rabbit femoral, iliac and renal arteries, and guinea-pig iliac artery.