In cell cultures of glial character derived from perinatal mouse brain adenosine elicits two effects. (a) At submicromolar concentrations I t inhibits the increase in the intracellular level of cyclic AMP caused by j-adrenoceptor agonists. (b) At concentrations above micromolar it increases the level of cyclic AMP in the cultures. These two effects are mediated by two different adenosine receptors present on the outer surface of the cells. This is concluded from the following evidence. (a) Both effects are antagonized by methylxanthines but not by blockage of adenosine uptake or inhibition of phosphodiesterase activity. (b) In both cases activity depends on the integrity of the ribose moiety of the nucleotide. Substituents of the purine system are tolerated comparatively well. (c) The order of potency of adenosine analogues is different for the two effects. We suggest the name A1 receptors for those that mediate the inhibition and A2 for those that mediate the stimulation of cyclic AMP accumulation.
Postembryonic development of plants is dependent on both intrinsic genetic programs and environmental factors. The plasticity of root hair patterning in response to environmental signals was investigated in the Columbia-0 wild type and 19 Arabidopsis mutants carrying lesions in various parts of the root hair developmental pathway by withholding phosphate or iron (Fe) from the nutrient medium. In the aging primary root and in laterals of the wild type, the number of root hairs increased in response to phosphate and Fe deficiency in a manner typical of each growth type. Although an increase in root hair density in -phosphorus plants was mainly achieved by the formation of extra hairs over both tangential and radial wall of underlying cortical cells, roots of -Fe plants were characterized by a high percentage of extra hairs with two tips. Root hair patterning and hair length was differentially affected by the presence or absence of phosphate and Fe among the genotypes under investigation, pointing to separate cascades of gene activation under all three growth conditions. Divergence in root hair patterning was most pronounced among mutants with defects in genes that affect the first stages of differentiation, suggesting that nutritional signals are perceived at an early stage of epidermal cell development. During elongation of the root hairs, no differences in the requirement of gene products between the growth types were obvious. The role of genes involved in root hair development in the aging primary root of Arabidopsis under the various growth conditions is discussed.
The new HES specification demonstrated favourable pharmacokinetic properties compared with other HES specifications of medium or high molecular weight. No clinically relevant plasma accumulation and related undesired effects on haemostasis are expected to occur under multiple-dose conditions.
Secretin stimulates the accumulation of cyclic AMP (half maximally stimulating concentration: 10-20 nM) in cultured mouse brain cells mainly consisting of glioblasts. Vasoactive Various peptides are known to be common to the brain and the gastrointestinal tract and pancreas (1). Some of these peptides (e.g., substance P, somatostatin, enkephalin) have been shown to elicit specific behavioral changes or changes in specific neuron firing rates or patterns (for review see refs. 2-4). They are, therefore, hypothesized to act on neurons as neuromodulators or neurotransmitters. Some neurohormones are also known to act on glial cells by regulating the intracellular level of cyclic AMP (for review see ref. 5). The possibility had to be considered that this would not only hold for biogenic amines such as norepinephrine but also for peptide hormones. Therefore, we investigated the effects of peptide hormones on the accumulation of cyclic AMP in glial cell cultures derived from neonatal mouse brain. We report-here that somatostatin inhibits the basal and the hormone-induced accumulation of cyclic AMP in such primary cultures. Furthermore, we report that the gastrointestinal hormones secretin and vasoactive intestinal peptide (VIP) stimulate the accumulation of cyclic AMP in these cultures, probably via different types of receptors. Thus a possible role of peptide hormones in the function of glial cells is indicated. In addition, the results suggest that secretin or a closely related compound might exert regulatory influence in the brain. A preliminary report of some of these results has been presented at a conference (6).MATERIALS AND METHODS Materials. Dulbecco's modified Eagle's medium and fetal bovine serum (GIBCO) were from C. Roth, Karlsruhe, Federal Republic of Germany. A partially purified preparation of VIP (porcine) was kindly donated by V. Mutt, Stockholm, Sweden. Isolated somatostatin (cyclic; bovine) was from Beckman,
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