ryanodine and inositol-1-3-4-5-tetrakisphosphate

The effects of age and chronic low-level lead exposure were studied on (a) [3H]IP3 and [3H]Ry binding to their respective receptors in brain membranes and (b) Ca2+ release from internal Ca2+ stores in brain synaptosomes obtained from the neonatal and adult rats. [3H]IP3 and [3H]Ry binding sites in the control-adult membranes were greater than those in the control-neonatal membranes. [3H]IP3 bound to a single high-affinity site, IP3-R. Ca2+ decreased [3H]IP3 binding to its receptor. [3H]Ry bound to at least four subspecies of Ry-Rs. KCl and IP3 increased, but Ca2+ caused a biphasic affect on [3H]Ry binding in brain membranes. IP1 and caffeine both caused greater increase in [Ca2+]I in the adult synaptosomes than the neonatal synaptosomes. IP4 redistributed Ca2+ from the caffeine-sensitive pool to the IP3-sensitive pool. IP3 increased the caffeine-induced mobilization of Ca2+ in synaptosomes. Chronic low-level lead exposure decreased the binding of [3H]IP3 to its receptors in membranes, attenuated the IP3-induced Ca2+ mobilization in synaptosomes, abolished the IP4-induced redistribution of Ca2+ from Ry sensitive Ca2+ store to IP3-sensitive Ca2+ store, and attenuated the effects of IP1 on [Ca2+]I in caffeine stimulated synaptosomes. Lead exposure, however, did not affect [3H]Ry binding to Ry-R in membranes or the caffeine-induced increase in [Ca2+]I in synaptosomes. Chronic lead exposure protected IP3-R against Ca(2+)-induced inhibition in membranes. This protection was greater in the neonatal samples than the adult samples. This suggests that chronic low-level lead exposure down-regulated the IP3-induced Ca2+ mobilization in synaptosomes without effecting the caffeine-induced Ca2+ mobilization.

Topics: Age Factors; Animals; Animals, Newborn; Binding Sites; Brain Chemistry; Caffeine; Calcium; Cell Membrane Permeability; Female; Inositol 1,4,5-Trisphosphate; Inositol Phosphates; Lead Poisoning; Pregnancy; Rats; Rats, Wistar; Ryanodine; Synaptosomes; Time Factors; Tritium

Injection of D-myo-inositol-1,4,5-trisphosphate (IP3) was found to induce a transient increase of intracellular Ca2+ concentration in cancerous mammary cells (MMT060562) and in normal mammary cells treated with epidermal growth factor. Responses to injection of either D-myo-inositol-1,4-bisphosphate (IP2) or D-myo-inositol-1,3,4,5-tetrakisphosphate (IP4) were small or absent. Furthermore, normal mammary cells cultivated with low-protein serum replacement alone or in the presence of differentiation-inducing hormones (insulin + cortisol + prolactin) were less sensitive to IP3. Thapsigargin induced a transient increase of Ca2+ due to the release of Ca2+ from an intracellular pool. There was no difference in the peak heights of the thapsigargin-induced Ca2+ increase when mammary cells were cultivated in the presence or absence of epidermal growth factor or insulin + cortisol + prolactin. These findings suggest that the releasable intracellular Ca2+ pool remained unchanged whereas sensitivity to IP3 increases during the proliferation stage. Mechanical stimulus of a mammary cell induces an increase of intracellular Ca2+ in the stimulated cell. A certain stimulating factor is released from the mechanically stimulated cell into the extracellular space, and it induces an increase of Ca2+ in surrounding cells. In contrast, the IP3-induced Ca2+ increase in both cancerous and epidermal growth factor-treated normal mammary cells did not spread to adjacent cells. Therefore, increase of Ca2+ is not sufficient to account for the release of stimulating substances from mammary cells in the mechanically-induced spreading response.

Topics: Animals; Caffeine; Calcium; Cell Division; Cells, Cultured; Drug Resistance; Epidermal Growth Factor; Epithelial Cells; Epithelium; Female; Inositol 1,4,5-Trisphosphate; Inositol Phosphates; Mammary Glands, Animal; Mammary Neoplasms, Experimental; Mice; Mice, Inbred ICR; Pregnancy; Ryanodine; Terpenes; Thapsigargin; Tumor Cells, Cultured