<b>Norepinephrine-induced Inositol 1,4,5-Trisphosphate Formation in Atrial Myocytes is Regulated by Extracellular Calcium, Protein Kinase C, and Calmodulin</b>

Abstract

SUMMARYWe investigated whether alteration of extracellular and intracellular Ca 2+ concentrations, protein kinase C, and calmodulin modulate norepinephrine(NE)-induced inositol 1,4,5-trisphosphate (IP 3 ) formation in neonatal rat atrial myocytes. NE-induced IP 3 production in atrial myocytes was stimulated by elevation of extracellular Ca 2+ in a dosedependent manner. However, TMB-8 (an intracellular calcium antagonist) and A23187 (an intracellular calcium agonist) did not significantly affect NE-induced IP 3 production. PMA (a protein kinase C agonist) significantly decreased and staurosporine (a protein kinase C antagonist) significantly stimulated NE-induced IP 3 production. W7 (a calmodulin antagonist) significantly increased the NE-induced IP 3 . In conclusion, elevation of extracellular Ca 2+ concentrations affects NE-induced IP 3 formation in atrial myocytes. Protein kinase C and calmodulin may control the IP 3 response to NE by a negative feedback mechanism. ( 2) The signal transduction of NE occurs through activation of phospholipase C (PLC), which leads to release of IP 3 . On the other hand, release of IP 3 by NE in atrial cells is also associated with the development of arrhythmias.3) Thus, NE-stimulated IP 3 plays an important role in atrial cells, however, intracellular regulation of NE-stimulated IP 3 formation in atrial myocytes remains unclear.

CRF Facilitates Calcium Release from Intracellular Stores in Midbrain Dopamine Neurons

“…Moreover, the actual release of calcium is regulated by multiple kinases (Fazal et al, 1998;Guerineau et al, 1991;Kim et al, 2007;Kuryshev et al, 1996;Lee and Tse, 1997;Luini et al, 1985;Spada et al, 1990;Takuma et al, 1994). Similar results are reported with CCK, serotonin, vasoactive intestinal peptide, neurotensin, vasopressin and norepinephrine (Belmeguenai et al, 2003;Gaisano et al, 1994;Kudoh et al, 2003;Petersen et al, 1994;Tse and Lee, 1998). The spatial and temporal properties of the increases in intracellular calcium, however, vary considerably with each hormone.…”

l-Carnitine rescues ketamine-induced attenuated heart rate and MAPK (ERK) activity in zebrafish embryos

“…The zebrafish embryo response to ketamine with regard to heart rate is concordant with that of the human infants [52] and non-human primate PND5 and 35 infants [19]. Differential effects of ketamine on heart rate in new born and adult humans has been attributed to the poorly developed sarcoplasmic reticulum of the neonatal myocardium [53], which appears to be more dependent on the entry of extracellular calcium rather than the release of calcium from intracellular sarcoplasmic reticulum [54]. It has also been shown that the p38 kinase inhibitor, SB 203580, reverses stress-induced myocardial dysfunction in vivo in rats [55].…”

Endothelium-dependent and independent effect of Guibourtia tessmannii (Caesalpiniaceae) on vascular contractility of rat

“…These substances act by activating intracellular and extracellular calcium; norepinephrine acting on intracellular calcium and KCl acting on extracellular calcium. In fact, depolarization related to K+ response leads to calcium input through L-type channels, which is a secondary route for NE, the main one being linked to activation of calcium stores by inositol-1, 4, 5-triphosphat [22] .…”