Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0406810 (NAME)
 13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The present study aimed to determine the influence of nitric oxide (NO) on the action of secretin in the cardiovascular system in intact rats. The studies involved the in vivo measurements of the systolic (SBP) and diastolic (DBP) blood pressure. The measurements were conducted when NO was absent, which was attained by the use of NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME), and when NO was in excess which was obtained by the administration of L-arginine (L-arg), the substrate for NO synthase or exogenous donor of NO, sodium nitroprusside (SNP). Secretin given at the following three doses: 0.75, 1.5 and 3.0 micromoles/kg iv increased SBP and DBP. L-NAME inhibited the slight hypertensive effect of secretin. L-arg abolished the hypertensive effect of the peptide given at the smallest dose, did not change the effect of secretin administered at the medium dose (which did not raise the pressure) and preserved the action of the highest secretin dose. SNP abolished the hypertensive effect of all doses of the peptide. In conclusion, the study has shown that both the lack and excess of NO change the in vivo effect of secretin in intact rats.
Pol J Pharmacol
PMID:Influence of nitric oxide on the cardiovascular action of secretin in intact rats. Part A. Does nitric oxide influence the effect of secretin on arterial blood pressure? 1133 29

The present study was designed to examine the effect of absence or excess of NO on secretin-mediated responses in the isolated heart. This problem was investigated using the modified Langendorff's method. Secretin administered at two higher doses increased the cardiac contraction amplitude (p < 0.05), but did not change the heart rate and coronary outflow. NO was depleted from experimental system by perfusion of the isolated heart with NO synthase inhibitor L-NAME (NG-nitro-L-arginine methyl ester) at 10 microM. It caused a significant decrease in coronary outflow (p < 0.01) and the tendency to bradycardia (p > 0.05) with no change in cardiac contraction amplitude. L-NAME abolished the positive inotropic effect of the medium secretin dose and preserved the inotropic effect of the highest dose of the peptide. It reversed the tendency to decrease coronary outflow induced by secretin (and L-NAME) given separately. To study the effect of NO excess, we applied the substrate for NO synthesis, amino acid L-arginine (L-arg) (100 microM) or exogenous donor of NO--sodium nitroprusside (SNP) (100 microM). Both substances did not affect the isolated heart function. L-arg did not change the effect of secretin, however it abolished non significant decrease in coronary outflow evoked by the highest dose of secretin. SNP preserved the positive inotropic action of the peptide and expressively reversed the negative values of coronary outflow observed after its co-administration with the highest dose of secretin. These results indicate that both the absence and excess of NO change the cardiac effect of secretin in the same direction.
Pol J Pharmacol
PMID:Influence of nitric oxide on the cardiovascular action of secretin in intact rats. Part B. Does nitric oxide influence the effect of secretin on isolated heart function? 1133 30

The effects of the class I metabotropic glutamate receptor (mGluR) stimulation on the behavioral activity of angiotensin II (Ang II) was investigated in the present study. The experiments were performed on adult male Wistar rats. Stimulation of the group I of mGluR receptors was evoked by icv injection of (S)-3,5-dihydroxyphenylglycine (3,5-DHPG) at the dose of 0.01 and 1 nmol per rat. Fifteen minutes later, the animals were given icv solution containing 1 nmol of Ang II. Memory motivated affectively was evaluated in passive avoidance and active avoidance responses (CARs). Moreover, the speculative influence of the treatment on anxiety and motor activity was tested in elevated plus-maze and in open field, respectively. We observed that both compounds did not have statistically significant influence on motor activity of rats in open field test. However, 3,5-DHPG at the dose of 0.01 nmol given alone and combined with Ang II tended to increase locomotor activity. 3,5-DHPG, given alone, significantly facilitated consolidation process in a passive avoidance situation (only at the dose of 0.01 nmol) but had no influence on acquisition and recall of information. Examination of the influence of 3,5-DHPG on the acquisition and extinction of CAR proved that it did not alter acquisition and extinction of these responses. In the elevated plus-maze, 3,5-DHPG had anxiogenic-like profile. Ang II, as repeatedly shown before, greatly increased passive avoidance latency, rate of acquisition of CARs and decreased their extinction. On the other hand, Ang II induced anxiolytic-like effect in elevated plus-maze. The pre-treatment of rats with 3,5-DHPG tended to attenuate behavioral effects of the Ang II administration.
Pol J Pharmacol
PMID:Examination of the influence of 3,5-DHPG on behavioral activity of angiotensin II. 1178 24

The inhibitory effect of lipopolysaccharides (LPS) on contraction evoked by alpha-adrenergic stimulation is quite well-known, but molecular mechanism of this inhibition is unclear. In the present study, an interaction between alpha-adrenoceptor response and LPS in rat tail artery was investigated using chemical stimulation. In the presence of LPS noradrenaline and phenylephrine, concentration-response curves were shifted to the right with a change in maximal responses. The K(A) and K(B) values calculated in the presence and absence of LPS did not differ significantly. The results strongly suggest that LPS did not change the affinity of alpha-adrenoceptors. Changes in the plot showing relationship between agonist-evoked responses and receptor occupancy in the presence of LPS and reduction of K(A)/ED50 value suggest reduction of alpha-adrenoceptor reserve. In the experiments performed on arteries without endothelium, the inhibitory effect of LPS was still present. In the presence of atropine, antazoline and indomethacin, the reduction of alpha-adrenoceptor reserve was noted, but in the presence of N-omega-nitro-L-arginine methyl ester (L-NAME), the inhibitory effect of LPS was not significant. Moreover, in LPS-pretreated arteries, in the presence of L-NAME, the increase in the receptor reserve was observed. It suggests that inhibitory effect of LPS is partially reversible. The results strongly indicate that in early endotoxemia, main inhibitory effect of LPS is connected with releasing nitric oxide and decreasing coupling between alpha1-adrenoceptor and signal induction.
Pol J Pharmacol
PMID:Pharmacometric analysis of alpha1-adrenoceptor function in rat tail artery pretreated with lipopolysaccharides. 1198 34

In contrast to the well-known Ah receptor-mediated regulation of the CYP1A1 gene by polycyclic aromatic hydrocarbons, the molecular mechanism by which phenobarbital (PB) and PB-like inducers affect transcription of CYP genes remains unknown; no receptor for these chemicals has been found to date. However, in the last 5 years PB-responsive sequences have been identified in the 5' flanking regions of several P450 genes. The phenobarbital-responsive enhancer unit (PBRU) of CYP2B gene family members contain two potential nuclear receptor binding sites (NR1 and NR2) that flank a nuclear factor 1 (NF-1) binding motif. The nuclear factors that regulate PBRU activity have not yet been characterized. It seems that PB may activate multiple nuclear orphan receptors to induce various CYP genes. CYP2B and CYP3A genes appear to be targets for the orphan receptors CAR and PXR, respectively. It is also possible that the pleiotropic effects of PB can, in part, be explained by the ability of the CAR-RXR heterodimer to bind to a variety of nuclear receptor binding motifs. The induction of cytochromes P450 may result in interactions between xenobiotics and in the interference of xenobiotic metabolism and endogenous signalling pathways.
Acta Biochim Pol 2000
PMID:Phenobarbital-induced expression of cytochrome P450 genes. 1199 99

The influence of nitric oxide (NO) on antinociceptive activity of diazepam (DZ), chlordiazepoxide (CDP) and clonazepam (CZ) was examined using the writhing test in mice. The effect of DZ was also studied in mice using hot plate and tail flick tests. DZ (1.25, 2.5 and 5 mg/kg), CDP (1.25, 2.5, 5, 10 and 20 mg/kg) and CZ (0.075, 0.3125, 0.625, 1.25 and 2.5 mg/kg) produced significant, dose-dependent (DZ, CDP) antinociception in mice. The benzodiazepines (BZs)-induced antinociception was antagonized by flumazenil (5 mg/kg) and was not changed by naloxone (2.5, 5 and 10 mg/kg), except that of CZ, which was reversed by 5 mg/kg of naloxone. NG-nitro-L-arginine methyl ester hydrochloride (L-NAME) as well as 7-nitroindazole (7-NI) intensified antinociceptive activity of BZs. The antinociceptive effect resulting from co-administration of L-NAME with CZ and 7-NI with CDP was reversed by L-arginine. Methylene blue (MB) increased, whereas L-arginine (but not D-arginine) decreased antinociceptive effects of the studied BZs. These results suggest that the NO-cGMP pathway is involved in the mechanism of BZs-induced antinociception in the writhing test in mice.
Pol J Pharmacol
PMID:Role of nitric oxide in benzodiazepines-induced antinociception in mice. 1202 41

The study was designed to investigate the role of the activation of class III metabotropic glutamate receptors (mGluRs) in the behavioral activity of angiotensin II (AngII). The experiments were performed on adult male Wistar rats. Stimulation of group III mGluRs was evoked by icv injection of agonist, L-2-amino-4-phosphonobutyric acid (L-AP4) (5 microl of 80 mM solution of L-AP4). Fifteen minutes later, the animals were given icv solution containing 1 nmol of AngII. Memory motivated affectively was evaluated by passive avoidance and active avoidance responses (CARs). Moreover, the speculative influence of the treatment on motor activity was tested in open field. We observed that both compounds did not have significant influence on motor activity of rats in open field test. L-AP4 given alone had no influence on acquisition, consolidation and recall of passive avoidance responses. Examination of influence of L-AP4 on the acquisition and extinction of CAR proved that this compound decreased acquisition of CARs, while it did not alter extinction of these responses. AngII, as repeatedly shown before, greatly increased passive avoidance latency, rate of acquisition of CARs and decreased they extinction. Pretreatment of rats with L-AP4 prevented all above behavioral effects of the AngII administration.
Pol J Pharmacol
PMID:L-AP4, a potent agonist of group III metabotropic glutamate receptor, decreases central action of angiotensin II. 1259 28

Recent evidence suggests that hypoxic pulmonary vasoconstriction (HPV) is mediated by hypoxia-induced closure of voltage-gated potassium channels in pulmonary vascular smooth muscle cells. It is also claimed that various vasoconstrictor mediators such as thromboxane A2 (TXA2), platelet activating factor (PAF), cysteinyl leukotrienes (cys-LTs) or endothelin-1 (ET-1) contribute to HPV. Their role, however, has not been unequivocally accepted. On the contrary, it is well known that endothelium-derived nitric oxide negatively modulates HPV. Since NO counteracts action of vasoconstrictor mediators, we tested the hypothesis that modulatory role of TXA2 PAF, cys-LTs and ET-1 in HPV would become apparent in absence of endogenous NO. For that purpose we assessed contribution of these mediators to HPV in the isolated blood-perfused rat lung pretreated with a non-selective NOS inhibitor, L-NAME. HPV, which was greatly augmented by L-NAME (300 microM) alone, was inhibited neither by a TXA2 synthase inhibitor (Camonagrel, 300 pM), nor by a PAF receptor antagonist (WEB 2170, 100 microM), nor by an inhibitor of five-lipooxygenase-activating protein (MK 886, 10 microM), nor by a non-selective ET-1 receptor antagonist (LU 302872, 30 pM). In summary, in isolated blood-perfused rat lung, TXA2, PAF, cys-LTs and ET-1 seem not to be involved in HPV, whereas we confirm the dominant role of endogenous NO in blunting HPV.
Pol J Pharmacol
PMID:Hypoxic pulmonary vasoconstriction in isolated blood-perfused rat lung; modulation by thromboxane A2, platelet-activating factor, cysteinyl leukotrienes and endothelin-1. 1259 30

The influence of nitric oxide (NO) on anticonvulsant activity of diazepam and clonazepam was examined in the pentetrazole- and electroshock-induced seizure models in mice. Protective efficacy of the threshold dose of diazepam against pentetrazole-induced clonic and tonic seizures, and death was significantly increased by NG-nitro-L-arginine methyl ester hydrochloride (L-NAME) while 7-nitroindazole (7-NI) was slightly less effective. The above intensifying effect of L-NAME on antiepileptic activity of diazepam was reversed by L-arginine, a substrate for NO formation, but not by D-arginine. Methylene blue, the guanylate cyclase inhibitor, increased the protective efficacy of diazepam and clonazepam in the pentetrazole-induced seizures. 7-NI was able to potentiate the protective efficacy of diazepam and clonazepam in electroshock-induced tonic hindlimb extension. These findings suggest that the cGMP/NO system may participate in antiepileptic effects of benzodiazepines.
Pol J Pharmacol
PMID:Role of nitric oxide in anticonvulsant effects of benzodiazepines in mice. 1292 45

Effect of intracerebroventricularly (icv) or subcutaneously (sc) injected L-arginine (L-Arg) on memory was determined using the procedure of passive avoidance test. Moreover, locomotor and exploratory activity was determined in rats in an open field test. We found that either the peripheral (sc) or icv administration of L-Arg significantly prolonged latency time in the passive avoidance test. This effect appeared at 20-100-fold higher doses in comparison to such effect of arginine vasopressin (AVP) observed in our previous study. This memory improving effect was not correlated with the inhibition of locomotor and exploratory activity. The effect of the lower icv dose (10 nmoles) of L-Arg was blocked by L-NAME, a non-selective nitric oxide synthase (NOS) inhibitor. Moreover, the effect of both used doses (10 and 100 nmoles) of L-Arg was also blocked by S-methylisothiourea (Mtu), a selective inhibitor of inducible isoform of NOS. On the other hand, the effect of higher icv dose of L-Arg (100 nmoles) was prevented by 7-nitroindazole (7-NI), an inhibitor of neuronal NOS. We conclude that a uniform effect of L-Arg on memory is mediated by different isoforms of NOS, mainly by neuronal and inducible NOS.
Pol J Pharmacol
PMID:Effect of L-arginine on memory in rats. 1473 93


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