Influence of salmeterol and benzalkonium chloride on G-protein-mediated exocytotic responses of rat peritoneal mast cells.

The long-acting beta(2)-adrenoceptor agonist salmeterol and the invert soap benzalkonium chloride share physicochemically important structures, namely a polar head group and a long aliphatic chain. Low concentrations of benzalkonium chloride have been shown to inhibit exocytotic responses in rat peritoneal mast cells by selectively interacting with heterotrimeric G-proteins of the G(i)-type. The present study investigates whether salmeterol inhibits, independently of beta-adrenoceptors, exocytotic responses of rat peritoneal mast cells induced by the direct agonists at G-proteins mastoparan or guanosine 5'-O-(3-thiotriphosphate) (++GTP gamma S++).

Short treatments of normotensive and hypertensive rats by angiotensin II and nitric oxide inhibitor induce an increase of noradrenaline sensitivity in isolated vena portae preparations.

The aim of the study was to examine the influence of a short-term treatment of conscious Wistar Kyoto rats (WKY) and stroke-prone spontaneously hypertensive rats (SHRSP) by angiotensin II (ANG II) and by ANG II in combination with either l -NAME, HOE 140 or minoxidil on the mean arterial blood pressure (MABP) and the noradrenaline sensitivity in isolated portal vein preparations. MABP was significantly increased by ANG II treatment and ANG II plus l -NAME. However, it was slightly affected by ANG II in association with HOE 140, and significantly lowered by ANG II plus minoxidil.

Cardioprotective effects of the Na(+)/H(+)-exchange inhibitor cariporide in infarct-induced heart failure.

Objective: We investigated the effect of chronic treatment with the new Na(+)/H(+)-exchange inhibitor, cariporide, on cardiac function and remodelling 6 weeks after myocardial infarction (MI) in rats.

Methods: Treatment with cariporide was commenced either 1 week pre or 30 min, 3 h, 24 h or 7 days after ligation of the left ventricular artery and was continued until haemodynamic parameters were obtained 6 weeks after MI in conscious rats.

Results: Compared to sham animals, untreated MI-controls developed pronounced heart failure after 6 weeks.

Selective expression of JNK isoforms and stress-specific JNK activity in different neural cell lines.

The function of c-Jun N-terminal kinases (JNKs) in the nervous system is poorly understood and the majority of the data has been gained in neuronal and non-neuronal cell lines. Thus, it is not clear to which extent the expression pattern and the degree of activation of the three JNK isoforms in different cell lines are representative for their activation in the adult brain. In the present study, the expression of JNK isoforms and the activity of JNK1 were determined following UV irradiation and exposure to H(2)O(2) and TNFalpha in three neural cell lines, rat PC12, murine Neuro2A and human SHSY5Y.

Dihydropyridine enantiomers block recombinant L-type Ca2+ channels by two different mechanisms.

1. The molecular basis of the state-dependent block of L-type Ca2+ channels by dihydropyridines is still poorly understood. Therefore, we studied the enantioselectivity of Ca2+ channel block by isradipine enantiomers at three holding potentials (-80, -60 and -40 mV) in Chinese hamster ovary (CHO) cells stably expressing the rabbit lung alpha1C-b-subunit.

Repetitive electroconvulsive seizures induce activity of c-Jun N-terminal kinase and compartment-specific desensitization of c-Jun phosphorylation in the rat brain.

Electroconvulsive seizures (ECS) are used for therapy of pharmacoresistent depression and are supposed to induce long-lasting neuronal alterations in morphology and gene expression. In this study, we have investigated the phosphorylation of the transcription factor protein c-Jun at its serine 73 residue by immunohistochemistry and the activity of the c-Jun N-terminal kinase 1 (JNK1) by immunocomplex assay following repetitive ECS in adult rats. In untreated controls, nuclear c-Jun immunoreactivity, but not N-terminal phosphorylation, was present in a variety of neuronal populations including the hippocampus, the temporobasal cortex and the amygdalar complex.

Inducible and constitutive transcription factors in the mammalian nervous system: control of gene expression by Jun, Fos and Krox, and CREB/ATF proteins.

This article reviews findings up to the end of 1997 about the inducible transcription factors (ITFs) c-Jun, JunB, JunD, c-Fos, FosB, Fra-1, Fra-2, Krox-20 (Egr-2) and Krox-24 (NGFI-A, Egr-1, Zif268); and the constitutive transcription factors (CTFs) CREB, CREM, ATF-2 and SRF as they pertain to gene expression in the mammalian nervous system. In the first part we consider basic facts about the expression and activity of these transcription factors: the organization of the encoding genes and their promoters, the second messenger cascades converging on their regulatory promoter sites, the control of their transcription, the binding to dimeric partners and to specific DNA sequences, their trans-activation potential, and their posttranslational modifications. In the second part we describe the expression and possible roles of these transcription factors in neural tissue: in the quiescent brain, during pre- and postnatal development, following sensory stimulation, nerve transection (axotomy), neurodegeneration and apoptosis, hypoxia-ischemia, generalized and limbic seizures, long-term potentiation and learning, drug dependence and withdrawal, and following stimulation by neurotransmitters, hormones and neurotrophins.

Angiotensin II and NGF differentially influence microtubule proteins in PC12W cells: role of the AT2 receptor.

Angiotensin AT2 receptors have been shown to play a role in cell differentiation characterized by neurite outgrowth in neuronal cells of different origin. To further investigate AT2 receptor-mediated events leading to neurite formation, we examined the effect of AT2 receptor stimulation on the microtubule components, beta-tubulin, MAP1B and MAP2, by Western blot analysis and immunofluorescence in quiescent and nerve growth factor (NGF)-differentiated PC12W cells. These proteins are involved in neurite extension and neuronal maturation.