Kaneda Takeharu, Watanabe Akitoshi, Shimizu Kazumasa, Urakawa Norimoto, Nakajyo Shinjiro
Division of Veterinary Pharmacology, Nippon Veterinary and Animal Science University, Japan.
J Vet Med Sci. 2005 Jul;67(7):659-65. doi: 10.1292/jvms.67.659.
The effects of various selective phosphodiesterase (PDE) inhibitors on muscle contractility and cyclic nucleotide contents in the guinea pig gall bladder were investigated. Various selective PDE inhibitors, vinpocetine (type 1), erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA, type 2), milrinone (type 3), Ro20-1724 (type 4), and zaprinast (type 5), inhibited CCh-induced contractions in a concentration-dependent manner. The rank order of potency for the gall bladder was Ro20-1724 > vinpocetine > EHNA > milrinone > zaprinast, which was different from that of the trachea, taenia coli, and aorta. In the presence of CCh (0.3 muM), vinpocetine, milrinone, and Ro20-1724 each increased cAMP content, but not cGMP. By contrast, zaprinast increased cGMP content, but not cAMP, and EHNA increased both cAMP and cGMP contents. These results suggest that vinpocetine-, milrinone-, and Ro20-1724-induced relaxation was correlated with cAMP, zaprinast-induced relaxation was correlated with cGMP, and that EHNA-induced relaxation was correlated with cAMP and cGMP in the guinea pig gall bladder. In conclusion, the effect of PDE inhibitors in the guinea pig gall bladder was different from those in smooth muscles, such as the trachea, taenia coli, and aorta.
研究了各种选择性磷酸二酯酶（PDE）抑制剂对豚鼠胆囊肌肉收缩性和环核苷酸含量的影响。各种选择性PDE抑制剂，长春西汀（1型）、赤藓红-9-（2-羟基-3-壬基）腺嘌呤（EHNA，2型）、米力农（3型）、Ro20-1724（4型）和扎普司特（5型），以浓度依赖性方式抑制乙酰胆碱（CCh）诱导的收缩。胆囊的效力排序为Ro20-1724>长春西汀>EHNA>米力农>扎普司特，这与气管、结肠带和主动脉不同。在存在CCh（0.3μM）的情况下，长春西汀、米力农和Ro20-1724各自增加cAMP含量，但不增加cGMP。相比之下，扎普司特增加cGMP含量，但不增加cAMP，而EHNA增加cAMP和cGMP含量。这些结果表明，长春西汀、米力农和Ro20-1724诱导的舒张与cAMP相关，扎普司特诱导的舒张与cGMP相关，并且EHNA诱导的舒张与豚鼠胆囊中的cAMP和cGMP相关。总之，PDE抑制剂在豚鼠胆囊中的作用与在气管、结肠带和主动脉等平滑肌中的作用不同。
