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Stromal cell-derived factor 1 (SDF-1) and the chemokine receptor CXCR4 are highly expressed in the nervous system. Knockout studies have suggested that both SDF-1 and CXCR4 play essential roles in cerebellar, hippocampal, and neocortical neural cell migration during embryogenesis. To extend these observations, CXCR4 signaling events in rat and human neural progenitor cells (NPCs) were examined. Our results show that CXCR4 is expressed in abundance on rat and human NPCs. Moreover, SDF-1alpha induced increased NPCs levels of inositol 1,4,5-triphosphate, extracellular signal-regulated kinases 1/2, Akt, c-Jun N-terminal kinase, and intracellular calcium whereas it diminished cyclic adenosine monophosphate. Finally, SDF-1alpha can induce human NPC chemotaxis in vitro, suggesting that CXCR4 plays a functional role in NPC migration. Both T140, a CXCR4 antagonist, and pertussis toxin (PTX), an inactivator of G protein-coupled receptors, abrogated these events. Ultimately, this study suggested that SDF-1alpha can influence NPC function through CXCR4 and that CXCR4 is functional on NPC., (Copyright 2004 Wiley-Liss, Inc.)

It has been suggested that the isolation and culture of human detrusor smooth muscle cells may provide useful insights into the physiology of the intact detrusor muscle. In the present paper, data are presented from cultured human bladder smooth muscle cells isolated from small, routinely available biopsies. Since the initiation of contractions involves a rise in intracellular Ca2+, this study has focused on the mechanisms involved in the rise of Ca2+ in cultured cells. Exposure of cells to bathing solutions with elevated K+ concentrations resulted in an increase in Ca2+ consistent with the presence of voltage-activated Ca2+ channels. Agonists, including carbachol, histamine and ATP, also activated repetitive transient increases in Ca2+ in the presence and absence of external Ca2+. Spontaneous Ca2+ transients were recorded in 31% of cells isolated from normal bladders. Such spontaneous and agonist-induced oscillations were not abolished in depolarized cells, suggesting that the mechanisms underlying the oscillations are not dependent on the cyclical operation of voltage-operated Ca2+ channels. However, the spontaneous activity was inhibited by the Ca2+ blocker verapamil, pointing to the presence of Ca2+ channels. The operation of an IP3-sensitive Ca2+ release mechanism was examined using saponin-permeabilized cells, which demonstrated that IP3 increased the rate of 45Ca2+ efflux. The conclusion from this study is that many of the mechanisms described in the intact tissue are operational in cultured cells.

The novelty of applying 3-dimensional graphic capabilities, involving area and vector changes was used to understand variations in inositol derivatives due to the systemic effects of large body surface area (BSA) burns. This report is an attempt to broaden current perspectives on how such changes in inositol forms impact on the disposition of IP3 within skeletal muscle cells. Because it is the first of its type to evaluate systemic effects in this way, it is called the alpha study. Consideration of multiple factors (viz., 5 orders of magnitude) involved in burn trauma in this manner provides new insight into the pharmacologic changes which utilize the IP3 signal transducing system that underlie burn trauma. Such insight would prove beneficial in improving the quality of rehabilitative burn care with respect to skeletal muscle physiology.

Enzymatic phosphatidylinositol-4,5-bisphosphate breakdown is not Ca(2+)-dependent in NG108-15 cells and the bradykinin-induced response consisted of at least two distinct components in the hybrid cells. The initial signal transduction from bradykinin receptors to acetylcholine secretion is composed of the inositol-1,4,5-trisphosphate-dependent Ca2+ pathway despite multiple pathways in the late phase.