Effect of Ca2+/calmodulin-dependent protein kinase II inhibitors on the neurogenic cerebroarterial relaxation

European Journal of Pharmacology
N TodaT Okamura

Abstract

In canine cerebral artery strips contracted with prostaglandin F2alpha, transmural electrical stimulation (5 Hz for 40 s) produced a relaxation which was abolished by tetrodotoxin. The neurogenic response was inhibited moderately by [S]-5-isoquinolinesulfonic acid,4-[2-[(5-isoquinolinyl-sulfonyl)methylamino]-3-oxo-(4-phenyl-1-piperazinyl)-propyl] phenyl ester (KN62), an inhibitor of Ca2+ /calmodulin-dependent protein kinase II, which however did not alter or only slightly reduced the relaxant response to electrical nerve stimulation in canine coronary arterial strips that is mediated via beta-adrenoceptors stimulated by norepinephrine. Nicotine-induced relaxation, mediated by nitric oxide (NO) derived from perivascular nerves, was also attenuated by KN62, whereas the response to exogenous NO was unaffected. The nicotine-induced increase in the cyclic GMP content in cerebral arteries was depressed by KN62. The neurogenic relaxation was not influenced by phorbol 12-myristate 13-acetate, an activator of protein kinase C. 8-Bromo-cyclic GMP and 8-bromo-cyclic AMP did not significantly alter the response to nerve stimulation. It is concluded that the phosphorylation pathway involving Ca2+/calmodulin-dependent protein kinase II, but ...Continue Reading

References

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Citations

Dec 15, 2000·European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology·S PogunE D London
Feb 24, 2001·Hypertension Research : Official Journal of the Japanese Society of Hypertension·T OkamuraN Toda
May 30, 2003·Pharmacological Reviews·Noboru Toda, Tomio Okamura
Feb 1, 2003·American Journal of Physiology. Heart and Circulatory Physiology·Jean-Christophe SchneiderA Tuan Dinh-Xuan
Jul 19, 2002·American Journal of Physiology. Heart and Circulatory Physiology·Jean-Christophe SchneiderA Tuan Dinh-Xuan

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