Akhtar R A, Abdel-Latif A A
Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta 30912-2100.
Eur J Pharmacol. 1991 Apr 25;206(4):291-5. doi: 10.1016/0922-4106(91)90112-u.
The effect of a cyclic GMP phosphodiesterase inhibitor, M & B 22948, on carbachol-induced phosphatidylinositol 4,5-bis-phosphate (PIP2) breakdown and phosphatidic acid labeling, 1,4,5-inositol trisphosphate (IP3) accumulation and muscle contraction was studied in bovine iris sphincter smooth muscle. Addition of carbachol (10 microM) to 32P-labeled tissue resulted in increased labeling of phosphatidic acid and hydrolysis of PIP2. In myo[3H]inositol labeled tissue, carbachol caused rapid accumulation of IP3 which reached its maximum at about 2 min. Under identical experimental conditions, carbachol initiated a rapid increase in muscle contraction (phasic component) which was followed by a slightly lower contractile response (tonic component) that lasted for several minutes. Pretreatment of the iris sphincter with M & B 22948 did not alter carbachol-stimulated PIP2 breakdown and phosphatidic acid labeling, IP3 accumulation, or phasic component of the contractile response. However, the tonic component of the contractile response was increasingly attenuated by increasing concentrations of the drug. In conclusion, the data presented demonstrate a close correlation between carbachol-induced IP3 accumulation and muscle contraction, and that M & B 22948 does not inhibit carbachol-induced responses in the iris sphincter.
在牛虹膜括约肌平滑肌中研究了环鸟苷酸磷酸二酯酶抑制剂M&B 22948对卡巴胆碱诱导的磷脂酰肌醇4,5-二磷酸（PIP2）分解、磷脂酸标记、1,4,5-肌醇三磷酸（IP3）积累及肌肉收缩的影响。向32P标记的组织中加入卡巴胆碱（10微摩尔）会导致磷脂酸标记增加和PIP2水解。在肌醇[3H]标记的组织中，卡巴胆碱可使IP3迅速积累，约2分钟时达到峰值。在相同实验条件下，卡巴胆碱会引发肌肉收缩迅速增强（相性成分），随后是持续数分钟的稍低收缩反应（紧张性成分）。用M&B 22948预处理虹膜括约肌不会改变卡巴胆碱刺激的PIP2分解、磷脂酸标记、IP3积累或收缩反应的相性成分。然而，随着药物浓度增加，收缩反应的紧张性成分逐渐减弱。总之，所呈现的数据表明卡巴胆碱诱导的IP3积累与肌肉收缩密切相关，且M&B 22948不抑制虹膜括约肌中卡巴胆碱诱导的反应。
