多种选择性磷酸二酯酶抑制剂对猪虹膜括约肌舒张及环核苷酸含量的影响

Effects of various selective phosphodiesterase inhibitors on relaxation and cyclic nucleotide contents in porcine iris sphincter.

作者信息

YOGO Takuya, KANEDA Takeharu, NEZU Yoshinori, HARADA Yasuji, HARA Yasushi, TAGAWA Masahiro, URAKAWA Norimoto, SHIMIZU Kazumasa

机构信息

Laboratory of Veterinary Surgery, Nippon Veterinary and Life Science University, Musashino, Tokyo, Japan.

出版信息

J Vet Med Sci. 2009 Nov;71(11):1449-53. doi: 10.1292/jvms.001449.

DOI:10.1292/jvms.001449

PMID:19959894

Abstract

The effects of various selective phosphodiesterase (PDE) inhibitors on muscle contractility and cyclic nucleotide contents in porcine iris sphincter were investigated. Forskolin and sodium nitroprusside inhibited carbachol (CCh)-induced contraction in a concentration-dependent manner. 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), also inhibited CCh-induced contraction in a concentration-dependent manner. The rank order of potency of IC(50) was zaprinast > Ro20-1724 > EHNA >/= milrinone > vinpocetine. In the presence of CCh (0.3 muM), vinpocetine, milrinone and Ro20-1724 increased cAMP, but not cGMP, contents. In contrast, zaprinast and EHNA both increased cGMP, but not cAMP, contents. This indicates that vinpocetine-, milrinone- and Ro20-1724-induced relaxation is correlated with cAMP, while EHNA- and zaprinast- induced relaxation is correlated with cGMP in porcine iris sphincter.

摘要

研究了各种选择性磷酸二酯酶（PDE）抑制剂对猪虹膜括约肌肌肉收缩性和环核苷酸含量的影响。福斯可林和硝普钠以浓度依赖性方式抑制卡巴胆碱（CCh）诱导的收缩。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），也以浓度依赖性方式抑制CCh诱导的收缩。IC（50）效力的顺序为扎普司特>Ro20-1724>EHNA≥米力农>长春西汀。在存在CCh（0.3μM）的情况下，长春西汀、米力农和Ro20-1724增加了cAMP含量，但未增加cGMP含量。相反，扎普司特和EHNA均增加了cGMP含量，但未增加cAMP含量。这表明在猪虹膜括约肌中，长春西汀、米力农和Ro20-1724诱导的舒张与cAMP相关，而EHNA和扎普司特诱导的舒张与cGMP相关。