Xestospongins (Xe's) A, C, D, araguspongine B, and demethylxestospongin B, a group of macrocyclic bis-1-oxaquinolizidines isolated from the Australian sponge, Xestospongia species, are shown to be potent blockers of IP3-mediated Ca2+ release from endoplasmic reticulum vesicles of rabbit cerebellum. XeC blocks IP3-induced Ca2+ release (IC50 = 358 nM) without interacting with the IP3-binding site, suggesting a mechanism that is independent of the IP3 effector site. Analysis of Pheochromocytoma cells and primary astrocytes loaded with Ca2+-sensitive dye reveals that XeC selectively blocks bradykinin- and carbamylcholine-induced Ca2+ efflux from endoplasmic reticulum stores. Xe's represent a new class of potent, membrane permeable IP3 receptor blockers exhibiting a high selectivity over ryanodine receptors. Xe's are a valuable tool for investigating the structure and function of IP3 receptors and Ca2+ signaling in neuronal and nonneuronal cells.

Background:The objective of this study was to characterize and quantitate the calcium responses to cholinergic stimulation in individual primary rat cortical astrocytes and human 132 1N1 astrocytoma cells. Materials and Methods:The fluorescent calcium probe Indo-1 AM and an attached cell analysis and sorting (ACAS) instrument were used to quantitate calcium responses in these cells. Results: A concentration-dependent response to carbachol was seen in both cell types. However, carbachol was more potent and efficacious, and the response was more homogeneous in the cell line. The calcium response was mediated by the M3 subtype of muscarinic receptors. Experiments in the absence of extracellular calcium and with EGTA demonstrated that the initial calcium spike

Ethanol neuro-behavioural teratogenesis was studied in the guinea pig because of its extensive prenatal brain development. Our objective was to study, in the offspring of the guinea pig, behavioural and hippocampal morphologic effects produced by chronic maternal administration of 3 and 4 g ethanol.kg body weight-1 x day-1. Pregnant guinea pig received one of the following chronic treatments via intubation into the oral cavity: 3 or 4 g ethanol.kg-1 x day-1 as two equally divided doses 2 h apart: isocaloric sucrose and pair feeding; or water. Five litters were obtained for each treatment. Locomotor activity rate was determined on postnatal days 10, 20, and 60, and testing of the spontaneous alteration task was conducted beginning on postnatal days 22 and 62. After behavioural testing, the hippocampus of the brain of randomly selected guinea pig offspring of each treatment group was assessed histologically by light microscopic examination of cresyl violet stained coronal sections. The 3 and 4 g ethanol.kg-1 x day-1 regimens did not restrict maternal body weight gain or growth of the offspring. Both regimens increased locomotor activity rate in the offspring, which persisted into adulthood for the 4 g ethanol.kg-1 x day-1 regimen. Neither ethanol regimen impaired spontaneous alternation, but the 4 g ethanol.kg-1 x day-1 regimen increased the percent completed trials. Only the 4 g ethanol.kg-1 x day-1 regimen produced structural injury in the hippocampus, consisting of a 25% decrease in the number of CA1 pyramidal neurons. The data demonstrate that the 4 g ethanol.kg-1 x day-1 regimen produces more behavioural dysfunction and hippocampal morphologic change compared with the 3 g ethanol.kg-1 x day-1 regimen.

Ethanol is a major health concern, with neurotoxicity occurring after both in utero exposure and adult alcohol abuse. Despite a large amount of research, the mechanism(s) underlying the neurotoxicity of ethanol remain unknown. One of the cellular aspects that has been investigated in relationship to the neuroteratogenicity and neurotoxicity of ethanol is the maintenance of calcium homeostasis. Studies in neuronal cells and other cells have shown that ethanol can alter intracellular calcium levels and affect voltage and receptor-operated calcium channels, as well as G protein-mediated calcium responses. Despite increasing evidence of the important roles of glial cells in the nervous systems, few studies exist on the potential effects of ethanol on calcium homeostasis in these cells. This brief review discusses a number of reported effects of alcohol on calcium responses that may be relevant to astrocytes' functions.

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