H-89 is a potent inhibitor of cyclic AMP-dependent protein kinase (protein kinase A) with IC50 of 48 nM and has weak inhibition on PKG, PKC, Casein Kinase, and others kinases.
H-89 inhibits protein kinase A, in competitive fashion against ATP. H-89 causes a dose-dependent inhibition of the forskolin-induced protein phosphorylation, with no decrease in intracellular cyclic AMP levels in PC12D cells. H-89 significantly inhibits the forskolin-induced neurite outgrowth from PC12D cells. H-89 (30 uM) inhibits significantly cAMP-dependent histone IIb phosphorylation activity in PC12D cell lysates[1]. H-89 (1-2 uM) significantly slows the repriming rate in rat skinned fibres, most likely due to it deleteriously affecting the T-system potential. H-89 (10-100 uM) inhibits net Ca2+ uptake by the SR and affectes the Ca32-sensitivity of the contractile apparatus in rat skinned fibres[2].
H-89 (0.2 mg/100g, i.p.) significantly increases seizure latency and threshold in PTZ-treated animals. H-89 (0.05, 0.2 mg/100 g, i.p.) prevents the epileptogenic activity of bucladesine (300 nM) with significant increase of seizure latency and seizure threshold[3].
H-89是环磷酸依赖性蛋白激酶（蛋白激酶A）的强效抑制剂，IC50为48 nM，对PKG、PKC、Casein Kinase和其他激酶的抑制作用较弱。
H-89以竞争性方式抑制蛋白激酶A，对ATP敏感。H-89导致剂量依赖性抑制丙酮肟诱导的蛋白磷酸化，在PC12D细胞中，细胞内环磷酸腺苷水平无明显下降。H-89显著抑制丙酮肟诱导的PC12D细胞神经突起生长。H-89（30微米）显著抑制PC12D细胞裂解液中cAMP依赖性的histone IIb磷酸化活性[1]。H-89（1-2微米）显著减缓大鼠剥离纤维的再兴奋速率，最可能是由于其对T系统电位的有害影响。H-89（10-100微米）抑制大鼠剥离纤维的SR净Ca2+吸收，影响肌原纤维的Ca32+敏感性[2]。
H-89（0.2毫克/100克，i.p.）显著增加PTZ处理动物的癫痫潜伏期和阈值。H-89（0.05、0.2毫克/100克，i.p.）预防了Bucladesine（300纳摩尔）的癫痫活性，显著增加了癫痫潜伏期和癫痫阈值[3]。
References:
[1]. Chijiwa T, et al. Inhibition of forskolin-induced neurite outgrowth and protein phosphorylation by a newly synthesized selective inhibitor of cyclic AMP-dependent protein kinase, N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide (H-89), of PC12D
[2]. Blazev R, et al. Effects of the PKA inhibitor H-89 on excitation-contraction coupling in skinned and intact skeletal muscle fibres. J Muscle Res Cell Motil. 2001;22(3):277-86.
[3]. Hosseini-Zare MS, et al. Effects of pentoxifylline and H-89 on epileptogenic activity of bucladesine in pentylenetetrazol-treated mice. Eur J Pharmacol. 2011 Nov 30;670(2-3):464-70.