Biomedical subjects

S Wurster

Publications and source records attributed to S Wurster.

5 recordsLinked to original sources

PubMed1991

Effect of fluoride, pertussis and cholera toxin on the release of arachidonic acid and the formation of prostaglandin E2, D2, superoxide and inositol phosphates in rat liver macrophages.

Fluoride elicited in liver macrophages a release of arachidonic acid and prostaglandins but not formation of inositol phosphates or superoxide. The effects of fluoride required extracellular calcium and were inhibited by staurosporine and by phorbol ester treatment of the cells. Furthermore, fluoride led to a translocation of protein kinase C from the cytosol to membranes. This indicates that the calcium-dependent protein kinase C is involved in the action of fluoride. Cholera toxin decreased the zymosan-induced release of arachidonic acid and prostaglandins but not of inositol phosphates or superoxide. Pertussis toxin ADP-ribosylated a 41,000 molecular weight membrane protein; enhanced specifically the zymosan-induced formation of prostaglandin(PG)E2 but did not affect the zymosan-induced release of arachidonic acid, PGD2, inositol phosphates or superoxide. These data suggest that activation of phospholipase (PL)A2, phosphoinositide (PI)-specific PLC and NADPH oxidase in liver macrophages is most probably not mediated by activation of guanine nucleotide binding (G)-proteins coupled directly to these enzymes.

Adenosine Diphosphate Ribose↗

PubMed1990

Regulatory proteins in presynaptic function.

Activation of alpha 2-adrenoceptors, opioid, A1-adenosine, and PGE receptors inhibited the stimulation-induced [3H]noradrenaline release in brain tissue in a concentration-dependent manner. Under experimental conditions (360 pulses/3 Hz) where the released noradrenaline activated the presynaptic alpha 2-autoreceptors, the effects of the heteroreceptor (k-opioid, A1-adenosine, PGE) agonists were decreased. By avoiding autoinhibition by either blockade of the alpha 2-autoreceptors with yohimbine or stimulating the tissue with four pulses/100 Hz, the heteroreceptor-mediated inhibition of [3H]noradrenaline release was markedly increased. The dependence of the heteroreceptor-mediated inhibition of evoked noradrenaline release on the extent of alpha 2-autoreceptor activation suggests a common postreceptor signal transduction pathway. PTX-catalyzed [32P]ADP ribosylation of synaptosomal membrane proteins revealed three bands of polypeptides with molecular weights corresponding to the alpha subunits of Go (39,000) and the Gi proteins (40,000, 41,000). Pretreatment with NEM reduced the PTX-induced 32P labeling by alkylating the alpha subunits at or near the site that is ADP ribosylated by PTX in a concentration-dependent manner. K(+)-evoked release of [3H]noradrenaline from synaptosomes indicated the presynaptic localization of the PTX-sensitive G proteins coupled to alpha 2-, k-, and A1-receptors of noradrenergic nerve terminals. Electrically evoked [3H]noradrenaline release was only increased by PTX or NEM in a time- and concentration-dependent manner when autoinhibition was present. The alpha 2-, opioid, and A1-adenosine receptor-mediated inhibition of [3H]noradrenaline release was impaired similarly by PTX or NEM treatment. In contrast, the inhibitory effect of PGE2 remained unaffected. These results indicate that presynaptic alpha 2-, opioid, and A1-receptors but not PGE receptors of noradrenergic nerve terminals are linked to PTX-sensitive G proteins. The interaction between the alpha 2-autoreceptors and the PGE receptors therefore does not occur at the level of a common pool of G proteins but at some subsequent step of the signal transduction mechanism.

Animals↗

PubMed1989

Effects of botulinum A toxin on presynaptic modulation of evoked transmitter release.

A possible influence of botulinum A toxin on the modulation of evoked neurotransmitter release was investigated in hippocampus tissue. Rabbit hippocampal slices prelabelled with [3H]noradrenaline ([3H]NA), [3H]5-hydroxytryptamine ([3H]5-HT) or [3H]choline were superfused with physiological medium and were stimulated electrically during superfusion. The evoked release of [3H]NA, [3H]5-HT and [3H]acetylcholine [( 3H]ACh) was inhibited by botulinum A toxin in a concentration- and time-dependent manner. Neither the inhibition of release of [3H]NA and [3H]5-HT by the alpha 2-adrenoceptor agonist clonidine nor facilitation of release in the presence of alpha 2-antagonists were influenced by pretreatment of the tissue with botulinum toxin. The toxin caused no [32P]ADP ribosylation of synaptosomal proteins of hippocampus. The facilitation of the stimulation-induced [3H]NA and [3H]5-HT release by the specific protein kinase C (PKC) activator 4 beta-phorbol-12,13-dibutyrate (PDB) was significantly diminished by botulinum A toxin. These results show that the evoked transmitter release is inhibited by botulinum A toxin by a mechanism which does not involve ADP ribosylation or an interaction with the alpha 2-adrenoceptor mechanism.

Acetylcholine↗

PubMed1988

P2-purinoceptor induced prostaglandin synthesis in primary rat astrocyte cultures.

Adenosine triphosphate (ATP) is one of the cotransmitters that are commonly released at catecholaminergic and cholinergic nerve terminals. The glial cell type most closely associated with the synapse is the astrocyte and, thus, is the next cellular element beside the postsynaptic neuron to face the transmitters released. This report gives evidence of P2-purinoceptors on cultured astroglial cells. Upon stimulation with nucleoside triphosphates and nucleoside diphosphates, the cells respond with synthesis of prostaglandins of the D2 type, which is the predominant prostaglandin made in rat brain. Nucleoside triphosphate analogues, such as 5'-adenyl-imido diphosphate, beta,gamma-methylene, or alpha,beta-methylene ATP were less effective than ATP or its non-hydrolysable analogue ATP [gamma S]. The receptor was desensitized by ATP [gamma S] within 15 min, whereas desensitization by alpha,beta-methylene ATP was significantly delayed. 8-phenyl-theophylline (10(-4) M) had no influence on ATP-stimulated prostaglandin synthesis. Adenosine 5'-monophosphate (AMP) and adenosine were unable to stimulate prostaglandin D2 formation. According to the common nomenclature for purinoceptors, the described astroglial receptor would fulfill the characteristics of a P2-purinoceptor. Furthermore, it is shown that pertussis toxin sensitive G-proteins influence some early step in prostaglandin synthesis. The inactivation of these proteins results in reduced prostaglandin formation. It is assumed that ATP serves as an important mediator in the cross-talk between neurons and astroglial cells at the synaptic cleft.

Adenosine Triphosphate↗

PubMed1988

Multiple pertussis toxin substrates as candidates for regulatory G proteins of adenylate cyclase coupled to the somatostatin receptor in primary rat astrocytes.

The involvement of G proteins in receptor mediated astroglial cAMP formation was studied. Isoproterenol or prostaglandin E2 stimulated adenylate cyclase of primary astroglial cells was inhibited by somatostatin. Preincubation of cells with increasing concentrations of islet activating protein (IAP) diminished somatostatin inhibition of adenylate cyclase. At an IAP concentration of 50 ng/ml somatostatin inhibition was completely abolished. Studies on IAP catalyzed 32P-ADP-ribosylation of astroglial cell particulate material revealed an incorporation of radiolabel into three polypeptides in the molecular weight range of 41,000-39,000 Dalton. Pretreatment of intact cells with IAP reduced radiolabeling of this molecular species in a concentration dependent manner. No further radiolabeling above background level was detectable after pretreatment of cultures with 10 ng IAP/ml or more. At present, the occurrence of at least three IAP substrates (G proteins) does not permit an identification of the somatostatin receptor coupled G protein. Rather, the finding reveals that astrocytes are endowed with multiple variants of GTP binding proteins likely to be coupled to different receptors.

Adenylate Cyclase Toxin↗