title: Norepinephrine-induced inositol 1,4,5-trisphosphate formation in atrial myocytes is regulated by extracellular calcium, protein kinase C, and calmodulin.
abstract: We investigated whether alteration of extracellular and intracellular Ca2+ concentrations, protein kinase C, and calmodulin modulate norepinephrine (NE)-induced inositol 1,4,5-trisphosphate (IP3) formation in neonatal rat atrial myocytes. NE-induced IP3 production in atrial myocytes was stimulated by elevation of extracellular Ca2+ in a dose-dependent manner. However, TMB-8 (an intracellular calcium antagonist) and A23187 (an intracellular calcium agonist) did not significantly affect NE-induced IP3 production. PMA (a protein kinase C agonist) significantly decreased and staurosporine (a protein kinase C antagonist) significantly stimulated NE-induced IP3 production. W7 (a calmodulin antagonist) significantly increased the NE-induced IP3. In conclusion, elevation of extracellular Ca2+ concentrations affects NE-induced IP3 formation in atrial myocytes. Protein kinase C and calmodulin may control the IP3 response to NE by a negative feedback mechanism.
authors.affiliation: Department of Anesthesiology, Hirosaki National Hospital, Hirosaki, Aomori, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Kudoh
authors.forename: Emiko
authors.initials: E
authors.lastname: Kudoh
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Katagai
authors.forename: Tomoko
authors.initials: T
authors.lastname: Takazawa
mesh_terms: D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D002147:Calmodulin / Q000378:metabolism / Q000502:physiology*; D005110:Extracellular Space / Q000378:metabolism; D006325:Heart Atria / Q000166:cytology; D015544:Inositol 1,4,5-Trisphosphate / Q000096:biosynthesis*; D007424:Intracellular Fluid / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism / Q000502:physiology*; D051381:Rats
chemical_list: D002147:Calmodulin; D015544:Inositol 1,4,5-Trisphosphate; D009320:Atrial Natriuretic Factor; D011493:Protein Kinase C; D002118:Calcium; D009638:Norepinephrine