Search PubMed⌕ Search

Biomedical subjects

C Allgaier

Publications and source records attributed to C Allgaier.

59 records · Page 4Linked to original sources
PubMed1986

Polymyxin B, a selective inhibitor of protein kinase C, diminishes the release of noradrenaline and the enhancement of release caused by phorbol 12,13-butyrate.

Slices of the rabbit hippocampus were labelled with 3H-noradrenaline, superfused continuously with a modified Krebs-Henseleit medium containing the uptake inhibitor cocaine and stimulated electrically (2 ms, 3 Hz, 24 mA, 5 V/cm). Phorbol 12,13-dibutyrate (PDB), a potent activator of protein kinase C (PKC), strongly enhanced the electrically-evoked overflow of tritium. In contrast, polymyxin B, a relatively selective inhibitor of PKC, diminished the evoked tritium overflow in a time- and concentration-dependent manner. The enhancement of the evoked overflow of tritium caused by PDB was strongly reduced in the presence of polymyxin B (100 mumol/l). These results suggest 1. that PKC may be involved in the physiological mechanism of action-potential-induced noradrenaline release from noradrenergic nerve terminals and 2. that the PDB-induced enhancement of noradrenaline release may be due to a direct activation of PKC.

Animals↗
PubMed1986

N-ethylmaleimide (NEM) diminishes alpha 2-adrenoceptor mediated effects on noradrenaline release.

The effect of N-ethylmaleimide (NEM), which has been shown to abolish rather selectively inhibition of adenylate cyclase, on the alpha 2-adrenoceptor-mediated modulation of noradrenaline release was studied. Slices of the rabbit hippocampus were loaded with 3H-noradrenaline, superfused continuously and stimulated twice electrically. NEM (30 mumol/l) applied for 30 min enhanced both basal and stimulation-evoked tritium overflow significantly. Occupation of the receptor by the alpha 2-adrenoceptor agonist clonidine prior to and during NEM treatment did not protect the alpha 2-adrenoceptor-mediated autoinhibitory feedback system from being affected by NEM. Preincubation of the hippocampal slices with NEM was without any influence on 3H-noradrenaline uptake. The inhibitory effect of clonidine on 3H-noradrenaline release was attenuated in a non-competitive manner. In addition, the facilitatory effect of the alpha 2-adrenoceptor antagonist yohimbine on the stimulus-evoked tritium overflow was reduced. The facilitation of the evoked noradrenaline release by yohimbine or yohimbine or yohimbine and NEM converged with increasing concentrations of yohimbine, suggesting that yohimbine and NEM were acting at the same signal-transduction system. These results are compatible with the idea that NEM, by alkylating the Ni-unit of a presynaptically located adenylate cyclase, prevents the alpha 2-adrenoceptor-mediated modulation of noradrenaline release.

Animals↗
PubMed1985

Islet-activating protein (pertussis toxin) diminishes alpha 2-adrenoceptor mediated effects on noradrenaline release.

The effect of islet-activating protein (IAP) on alpha 2-adrenoceptor mediated modulation of noradrenaline release in the rabbit hippocampus was studied. Slices of the hippocampus were incubated for 6 h with IAP, subsequently loaded with 3H-noradrenaline and superfused continuously. IAP-pretreatment significantly enhanced the electrically evoked transmitter release and diminished the facilitatory effect of the alpha 2-adrenoceptor antagonist yohimbine. In addition, the inhibitory effect of the alpha 2-adrenoceptor agonist clonidine was reduced. These results provide circumstantial evidence that an inhibitory guanine-nucleotide-binding protein, most probably Ni of a presynaptically located adenylate cyclase, is involved in the alpha 2-autoreceptor mediated modulation of noradrenaline release.

Adenylate Cyclase Toxin↗
PubMedDate not supplied

Staurosporine counteracts the phorbol ester-induced enhancement of neurotransmitter release in hippocampus.

The effects of staurosporine, introduced as a very potent inhibitor of protein kinase C (PKC), on evoked neurotransmitter release were investigated and compared with those of the other PKC inhibitors: 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H7) and polymyxin B (PMB). Slices of rabbit hippocampus, prelabelled with either [3H]noradrenaline, [3H]5-hydroxytryptamine or [3H]choline were superfused with physiological medium. During superfusion the slices were stimulated either electrically (3 Hz, 5 V/cm, 24 mA, 2 msec) or by high K+ (30 mM) for 2 min, respectively. Both the electrically and potassium evoked overflow were increased by the PKC activator 4 beta-phorbol 12,13-dibutyrate (PDB). The degree of the enhancement by PDB was dependent on the transmitter and the stimulation conditions used. These results may be explained by differences in the extent of activation of PKC during electrically or potassium evoked release. The PDB-induced enhancement of electrically or potassium evoked release of the 3 transmitters was counteracted by staurosporine (1 microM) in concentrations much lower than those required for H7 (100 microM) and PMB (100 microM). PMB, which has been shown to decrease electrically evoked transmitter release, similarly diminished K+-evoked release. In contrast, only the potassium evoked [3H]acetylcholine release was significantly diminished by staurosporine (1 microM) and H7 (100 microM). In conclusion, these results show again that facilitation of neurotransmitter release by phorbol esters is due to activation of PKC.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗