Search results for "phosphodiester"
showing 10 items of 176 documents
Selective action of two aporphines at alpha 1-adrenoceptors and potential-operated Ca2+ channels.
1993
Abstract Contractions evoked by noradrenaline (1 μM) or a depolarizing solution of 60 mM KCI were concentration dependently depressed by the aporphine alkaloids (S)-boldine and (R)-apomorphine in rataorta. Both drugs had a greater inhibitory potency on the contraction elicited by noradrenaline. Dose-response curves for noradrenaline were shifted to the right in presence of (S)-boldine. (R)-Apomorphine acted by a complex mechanism at α 1 -adrenoceptors and its inhibitory effects was irreversible. The conformational features of these alkaloids may explain their different behaviour at α 1 -adrenoceptors. In Ca 2+ -free solution, the alkaloids inhibited the contraction evoked by noradrenaline b…
Multiple actions of glaucine on cyclic nucleotide phosphodiesterases, α1-adrenoceptor and benzothiazepine binding site at the calcium channel
1992
1. In the present study, the properties of glaucine (an aporphine structurally related to papaverine) were compared with those of papaverine, diltiazem, nifedipine and prazosin. The work includes functional studies on rat isolated aorta contracted with noradrenaline, caffeine or KCl, and a determination of the affinity of glaucine at calcium channel binding sites of alpha-adrenoceptors, by use of [3H]-(+)-cis-diltiazem, [3H]-nitrendipine and [3H]-prazosin binding to cerebral cortical membranes. The effects of glaucine on the different molecular forms of cyclic nucleotide phosphodiesterases (PDE) isolated from bovine aorta were also determined. 2. Contraction evoked by noradrenaline (1 micro…
Investigations of the dual contractile/relaxant properties showed by antioquine in rat aorta.
1993
1. In the present study we assessed the activity of antioquine, a bisbenzyltetrahydroisoquinoline alkaloid isolated from Pseudoxandra sclerocarpa, by examining its effects on the contractile activity of rat isolated aorta, specific binding of [3H]-(+)-cis-diltiazem, [3H]-nitrendipine and [3H]-prazosin to cerebral cortical membranes and the different molecular forms of cyclic nucleotide phosphodiesterases (PDE) isolated from bovine aorta. 2. Contractions in rat aorta induced by high concentrations of KCl (80 mM) and noradrenaline (1 microM) were inhibited by antioquine in a concentration-dependent manner (0.1 microM- 300 microM). The alkaloid appeared more potent against KCl-induced contract…
Adrenergic modulation of the release of 5-hydroxytryptamine from the vascularly perfused ileum of the guinea-pig
1988
1. Isolated segments of the guinea-pig ileum were vascularly perfused and the release of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) into the portal venous effluent was determined by h.p.l.c. with electrochemical detection. Test substances were applied via the arterial perfusion medium. 2. Isoprenaline (0.1 microM) increased the outflow of 5-HT and 5-HIAA maximally by about 75% and this was antagonized by propranolol (0.1 microM). Forskolin (1-10 microM) increased the outflow of 5-HT by approximately 105% and that of 5-HIAA by approximately 55%. The phosphodiesterase inhibitor AH 21-132 (0.1-1 microM) increased the outflow of 5-HT and 5-HIAA by about 70%. Isoprenaline…
Alternative splicing of SMPD1 in human sepsis.
2015
Acid sphingomyelinase (ASM or sphingomyelin phosphodiesterase, SMPD) activity engages a critical role for regulation of immune response and development of organ failure in critically ill patients. Beside genetic variation in the human gene encoding ASM (SMPD1), alternative splicing of the mRNA is involved in regulation of enzymatic activity. Here we show that the patterns of alternatively spliced SMPD1 transcripts are significantly different in patients with systemic inflammatory response syndrome and severe sepsis/septic shock compared to control subjects allowing discrimination of respective disease entity. The different splicing patterns might contribute to the better understanding of th…
Phosphodiesterase 10A in the Rat Pineal Gland: Localization, Daily and Seasonal Regulation of Expression and Influence on Signal Transduction
2010
The cyclic nucleotide phosphodiesterase 10A (PDE10A) is highly expressed in striatal spiny projection neurons and represents a therapeutic target for the treatment of psychotic symptoms. As reported previously [J Biol Chem 2009; 284:7606–7622], in this study PDE10A was seen to be additionally expressed in the pineal gland where the levels of PDE10A transcript display daily changes. As with the transcript, the amount of PDE10A protein was found to be under daily and seasonal regulation. The observed cyclicity in the amount of PDE10A mRNA persists under constant darkness, is blocked by constant light and is modulated by the lighting regime. It therefore appears to be driven by the master cloc…
Evaluation of an alternative dosing regimenwith tadalafil, three times per week, for men with erectile dysfunction: SURE study in Italy.
2007
AIM: To examine the preference for two dosing regimens of 20 mg of tadalafil, on demand or three times per week, in men affected with erectile dysfunction (ED) in Italy. METHODS: Scheduled Use versus on demand Regimen Evaluation (SURE) is a multicenter, crossover and open-label study, involving 94 urology centers in Italy. Patients aged 18 years or older affected with ED for at least 3 months were enrolled and randomized to 20 mg of tadalafil treatment on demand or three times per week for 5-6 weeks. After a 1-week washout, patients were crossed over to the alternate regimen for 5-6 weeks. A treatment preference question was used to determine the preferred treatment regimen. International I…
The effect of S-(+)-boldine on the α1-adrenoceptor of the guinea-pig aorta
1996
1. The cardiovascular activity of S-(+)-boldine, an aporphine alkaloid structurally related to papaverine, was determined. The work includes functional studies on guinea-pig isolated aorta contracted with noradrenaline, caffeine, KCl or Ca2+, and on guinea-pig trachea contracted with acetylcholine or histamine. 2. S-(+)-boldine inhibited in a concentration-dependent manner the contractile response evoked by noradrenaline (10 microM) in guinea-pig aorta (IC50 = 1.4 +/- 0.2 microM) while the KCl depolarizing solution (60 mM)- or the Ca2+ (1 mM)-induced contractions were only partially affected by boldine up to 300 microM. In contrast, papaverine relaxed noradrenaline (NA), KCl or Ca2+ induced…
Role of K+ and Ca2+ fluxes in the cerebroarterial vasoactive effects of sildenafil
2007
The aim of this study was to assess the role of K(+) and Ca(2+) fluxes in the cerebroarterial vasoactive effects of the phosphodiesterase-5 inhibitor sildenafil. We used isolated rabbit basilar arteries to assess the effects of extracellular K(+) raising on sildenafil-induced vasodilatation, and studied the pharmacological interaction of sildenafil with selective modulators of membrane K(+) and Ca(2+) channels. Expression of Kv1 subunits of K(+) channels was assessed at messenger and protein levels. Parallel experiments were carried out with zaprinast for comparison. Sildenafil (10 nM-0.1 mM) induced concentration-dependent relaxation of endothelin-1 (10 nM)-precontracted arteries, which wa…
Gastric relaxation induced by apigenin and quercetin: Analysis of the mechanism of action
2009
Abstract Aims Recently, flavonoids have been shown to cause murine gastric relaxation. In the present study we examined the mechanism of action underlying gastric relaxation induced by apigenin and quercetin in isolated mouse stomach. Main methods The mechanical activity from the whole stomach was detected as changes in the endoluminal pressure and the response to increasing concentrations of both flavonoids were tested before and after different pharmacological treatments. Key findings Apigenin and quercetin-induced a concentration-dependent gastric relaxation, apigenin being more potent than quercetin. The responses were unaffected by 2′5′dideoxyadenosine, an inhibitor of adenylate cyclas…