Inhibitory effects of several calcium channel blockers and papaverine on 「^^3 H」-prazosin and 「^^3 H」-yohimbine binding to membranes of respective rat kidney and canine platelets

• Published in: Japanese Journal of Pharmacology 1986, Vol.40 (suppl), p.201-201
• Main Authors: Naoki OHara, Hiroshi Ono, Koroku Hashimoto
• Format: Article
• Language: Japanese
• ISSN: 0021-5198

We compared inhibitory effects of diltiazem, nifedipine, perhexiline, verapamil and papaverine on specific 「^^3 H」-prazosin (H-P) binding to rat kidney membranes and on 「^^3 H」-yohimbine (H-Y) binding to canine platelet membranes. The membranes were incubated with 0.9-1.3 nM of H-P or with 2-4 nM of H-Y for 30 min at 25℃ in the presence of severalconcentrations of the drugs. Verapamil inhibited the specific binding of both ligands most effectively compared to other drugs. The inhibitory potency of these drugs for specific binding of both ligands ranked as follows ; verapamil＞perhexiline＞papaverine＞dil-tiazem＞nifedipine. The stereo-isomers of verapamil had similar potency (K_I =0.8-1.0 μM) in the inhibition of H-P binding. However, H-Y binding was stereo-specificially inhibited by (-)-verapamil ( K_I =0.12±0.02 μM) and (+)-verapamil (K_I =0.74±0.1 μM). Papaverine, a parent compound of verapamil, inhibited specific binding of both ligands with K_I of 9±2 μM and 15 ± 0.1 μM for H-P and H-Y, respectively. Although the affinities of verapamil to the binding sites of both ligands were rather low, effects of verapamil on alpha-adrenoceptors may concern to its unique pharmacological profile among calcium channel blockers used. Effects of papaverine on alpha-adrenoceptors may play a role in the inhibiton of slow calcium channels by high concentration of this compound where alpha-adrenoceptor-mediated calcium channels exist.