RESUMO
We have investigated the pharmacological properties of pteleprenine, a quinoline alkaloid, on contractile responses of the guinea-pig ileum and on inotropic responses of the canine left atrium. Although pteleprenine (0.1-1 microM) had no effect on the contraction of the ileum induced by acetylcholine at 10 microM it significantly inhibited acetylcholine-induced contraction of the ileum. Pteleprenine (0.1-10 microM) reduced nicotine induced-contraction of the ileum in a concentration-dependent manner yet had no maximum relaxant effect even at a concentration of 10 microM. From Schild analysis the pA2 of pteleprenine on the guinea-pig ileum was found to be 6.6. The contraction of the ileum induced by 10 microM 1,1-dimethyl-4-phenylpiperazinium, a specific agonist of nicotinic acetylcholine receptors, was concentration-dependently suppressed by 10 nM-10 microM pteleprenine. In contrast, 0.1-10 microM pteleprenine did not antagonize the acetylcholine- and nicotine-induced negative inotropic contractile responses of the canine left atrium. These results show that pteleprenine has inhibitory action against nicotinic acetylcholine receptors in the guinea-pig ileum but not in the canine left atrium. Our findings also suggest that pteleprenine might be a novel lead compound as a nicotinic receptor antagonist.
Assuntos
Dioxóis/farmacologia , Átrios do Coração/efeitos dos fármacos , Íleo/efeitos dos fármacos , Contração Miocárdica/efeitos dos fármacos , Antagonistas Nicotínicos/farmacologia , Plantas Medicinais , Quinolonas/farmacologia , Acetilcolina/farmacologia , Animais , Iodeto de Dimetilfenilpiperazina/farmacologia , Cães , Relação Dose-Resposta a Droga , Feminino , Cobaias , Átrios do Coração/metabolismo , Íleo/metabolismo , Japão , Masculino , Contração Muscular/efeitos dos fármacos , Nicotina/farmacologia , Agonistas Nicotínicos/farmacologiaRESUMO
We investigated the pharmacological properties of pteleprenine, a quinoline alkaloid contained in the Rutaceous plant, Orixa japonica, on the contractile responses of the guinea pig ileum and on the inotropic responses of the canine left atrium. Contractile responses of the ileum to acetylcholine and histamine were not inhibited by less than 10(-6) M of pteleprenine. Meanwhile, the nicotine induced-contraction of the ileum was dose-dependently diminished by pteleprenine, but the contractile response to nicotine did not reach the maximum value in the presence of 10(-5) M of pteleprenine. The pA2 value of pteleprenine was 6.6 as determined from the Schild plot, which slope was nearly unity. Furthermore, the contraction of the ileum by 10(-5) M of 1,1-dimethyl-4-phenylpiperazinium (DMPP), a specific agonist of nicotinic acetylcholine receptors, was also dose-dependently suppressed by pteleprenine. On the other hand, 10(-5) M of pteleprenine did not have considerable inhibitory effects on acetylcholine- and nicotine-induced negative inotropic effects in the canine left atrium. From these results, it is suggested that pteleprenine has a specific inhibitory effect on nicotinic acetylcholine receptors in the guinea pig ileum.