Effects of ketanserin and 3-[2-[4-(o-methoxyphenyl)-1-piperazinyl]ethyl]-2,4(1H,3H)- quinazolinedione monohydrochloride (SGB-1534), anti-hypertensive agents, on 3H-serotonin and 3H-ketanserin bindings to serotonergic (5HT1 and 5HT2) receptors in dog brain and aorta.

Abstract

Serotonin has an important role in the control of blood pressure, because serotonin2 (5HT2) antagonists ameliorate hypertension. The 5HT2 antagonistic action may be due in part to α1-adrenoceptor blocking action. Thus, the presetn study was designed to examine the effects of 5HT2 antagonists (ketanserin and cinanserin) and α1-antagonists (SGB-1534, 3-[2-[4-(o-methoxyphenyl)-1-piperazinyl]ethyl]-2, 4(1H, 3H)-quinazolinedione monohydrochloride, and prazosin) on the 3H-5-hydroxytryptamine creatine sulfate (3H-serotonin) and 3H-ketanserin bindings to serotonin1 (5HT1) receptors in the dog brain and 5HT2 receptors in the dog brain and aora by using the radioligand binding assay method. The existence of 3H-ketanserin binding sites was definitely observed in the dog brain and aorta. The Kd and Bmax values of 3H-ketanserin binding to 5HT2 receptors in the dog aorta were 1.20 nM and 36 fmol/mg protein, respectively. 5HT1 and 5HT2 receptors also existed in the dog brain. Inhibition of 3H-ketanserin bindings by ketanserin and cinanserin in the dog brain and aorta was observed at very low concentrations, but inhibition by SGB-1534 and prazosin was observed only at very high concentrations. Furthermore, inhibitions of 3H-serotonin binding by ketanserin and prazosin were observed at high concentrations, but the Ki value of SGB-1534 was found to be 371 nM, These results suggest that 5HT2 antagonists and α1 adrenoceptor antagonists have different effects on the 3H-ketanserin bindings to 5HT2 receptors in the aorta and that hypotensive effect of 5HT2 antagonists may be largely concerned with 5HT2 receptors. On the other hand, that of α1-antagonists may be due to α1-adrenoceptor blocking action in vascular tissues as described previously.