The role of the angiotensin AT1 receptors in certain behavioural effects of angiotensin II (Ang II), using their selective antagonist losartan (DuP 753), was assessed. Ang II, given intracerebroventricularly (ICV) at the dose of 1 nmole, significantly improved object recognition, learning of conditioned avoidance responses (CARs), and recall of a passive avoidance behaviour. Losartan alone (1 microgram) was ineffective in any test except for the elevated 'plus' maze measuring anxiety which was diminished by the drug, both in peptide treated and in control rats. Losartan, given 5 min before Ang II, abolished improved after the peptide recall of the passive avoidance and object recognition. Losartan did not influence increased after Ang II rate of CARs acquisition. None of the treatments significantly changed behaviour of rats in the open field. The results point to the considerable involvement of the AT1 angiotensin receptors in the cognition improving effects of Ang II. However, unspecific psychoactivity of losartan should also be taken into account.

Angiotensin II↗

PubMedDate not supplied

Effect of angiotensin II and saralasin on motor activity and the passive avoidance behavior of rats.

One nmole of angiotensin II (ANG II) or saralasin, given intracerebroventricularly, failed to alter the motor activity of rats in open field. A combined injection of both peptides caused a significant decrease of the number of crossings and rearings. In the electromagnetic motimeter horizontal activity of animals was changed by neither of the peptides while the vertical activity was increased by ANG II. Again, a combined injection of saralasin and ANG II inhibited both horizontal and vertical activity. Stereotypies evoked by both apomorphine (2 mg/kg) and amphetamine (6.5 mg/kg), given intraperitoneally, were markedly intensified by ANG II and saralasin. A five-fold increase of the re-entry latencies in the passive avoidance situation was observed after pre-test administration of ANG II or saralasin but not the two in combination. These results suggest that ANG II and saralasin may improve processes related to learning and memory through an unspecific mechanism involving central dopamine systems.

Angiotensin II↗

PubMedDate not supplied

Synthesis of new chiral peptide nucleic acid (PNA) monomers.

We have synthesised a series of new chiral type I peptide nucleic acid monomers in total yields of 36-53%, derived from Val, Ile, Ser(Bzl), Pro, and Trp, employing convenient procedure.

Peptide Nucleic Acids↗

PubMedDate not supplied

Studies on the central activity of kinins.

The influence of bradykinin and kallikrein on the levels of noradrenaline (NA), dopamine (DA) and serotonin (5-HT) as well as the influence of bradykinin on the levels of normetanephrine, homovanillic (HVA) and 5-hydroxyindoleacetic (5-HIAA) acids were investigated in different parts of the brain (cerebellum, corpus striatum, cortex, hippocampus, hypothalamus, medulla oblongata and midbrain). Kinins decrease the levels of NA and DA and their metabolites, and increase the level of 5-HT and 5-HIAA, expecially in corpus striatum and hypothalamus. The results of these investigations correlate with previously reported behavioural effects of kinins.

Animals↗

PubMedDate not supplied

Effect of angiotensin on the central action of dopamine.

Angiotensin given intraventricularly enhances amphetamine but not apomorphine-induced stereotypy 30 min. after peptide administration. Simultaneous injection of angiotensin and dopamine increases amphetamine -- while decreases apomorphine -- induced stereotypy. The stereotypy produced either by apomorphine or amphetamine in rats pretreated with Ro 4-4602 + L-DOPA was diminished by angiotensin. Angiotensin elevated haloperidol-induced catalepsy. A possibility that angiotensin may inhibit both release and uptake of dopamine by nerve endings is discussed.

Amphetamine↗

PubMedDate not supplied

Influence of albumin degradation products (ADP) on the central action of catecholamines.

The influence of ADP on the central action of catecholamines was investigated. ADP abolished the central action of noradrenaline, amphetamine and nialamide. The peptides decreased apomorphine stereotypy and enhanced haloperidol induced catalepsy. These results support our previous suggestions [10-14] that ADP acts on the CNS by antagonizing the action of central catecholamines.

Albumins↗

PubMedDate not supplied

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?

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.

Animals↗

PubMedDate not supplied

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?

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.

Animals↗

PubMedDate not supplied

3,5-DHPG influences behavioral effects of baclofen in rats.

The role of 3,5-DHPG, an agonist of group I metabotropic glutamate receptors (I mGluRs) in certain behavioral effects of baclofen, an agonist of GABA-B receptor, was assessed. Baclofen, given intraperitoneally (ip) at the dose of 0.25 mg/kg, enhanced the number of crossings and bar approaches in the open field and was ineffective in the passive avoidance tests, and it prolonged time spent in closed arms and shortened time spent in open arms, reduced number of entries into open arms in the elevated "plus" maze, measuring anxiety. 3,5-DHPG given intracerebroventricularly (icv) alone at doses of 0.01, 0.1 and 1.0 nmole did not change locomotor activity in the open field test, except bar approaches: when 3,5-DHPG was given at the dose of 0.01 nmole it enhanced the activity of rats. At doses of 0.01 and 1.0 nmole it improved, but at the dose of 0.1 nmole it significantly impaired retrieval in the passive avoidance situation. All used doses of 3,5-DHPG did not influence the time spent in closed or open arms and the number of entries into open or closed arms in the elevated "plus" maze. 3,5-DHPG, given at the doses of 0.01, 0.1 and 1.0 nmole 10 min after baclofen significantly changed the effect of baclofen decreasing crossings and rearings in the open field, while 3,5-DHPG used at the doses of 0.01 and 1.0 nmole in rats pretreated with baclofen reduced bar approaches. Rats which received baclofen and, 10 min later, 3,5-DHPG at doses of 0.1 and 1.0 nmole, showed significantly improved retrieval in the passive avoidance response. The effect of 3,5-DHPG and baclofen were changed, i.e. 3,5-DHPG and baclofen can cooperate in retrieval process. Coadministration of baclofen and 3,5-DHPG at the dose of 1.0 nmole reduced time spent in the open arms in comparison with baclofen, i.e. this dose of 3,5-DHPG changed the effect of baclofen evaluated in the "plus" maze. Summary, the activation of I mGluR by 3,5-DHPG modulates GABA-B neurotransmission stimulated by baclofen, which is reflected by changing behavioral activity of rats.

Animals↗

PubMedDate not supplied

Examination of the influence of 3,5-DHPG on behavioral activity of angiotensin II.

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.

Angiotensin II↗

PubMedDate not supplied

AIDA influences behavior in rats pretreated with baclofen.

The influence of the blockade of group I metabotropic glutamate receptors (I mGluRs) by AIDA on some behavioral effects of rats pretreated with baclofen, an agonist of GABA-B receptor, was investigated using behavioral tests: the open field, the passive avoidance response and the elevated "plus" maze. Baclofen, applied intraperitoneally (ip) at a dose of 0.25 mg/kg, increased the number of crossed fields and bar approaches in rats in the open field test, and prolonged the time spent in the closed arms, shortened the time spent in the open arms and decreased the number of entries to the open arms in the elevated "plus" maze, but did not affect retrieval in the passive avoidance response. AIDA administered intracerebroventricularly (icv) alone at a dose of 100 nmol reduced crossings and rearings in the open field test, however, it had no effect on retrieval in the passive avoidance situation, nor did it show any influence in the elevated "plus" maze. AIDA given 15 min after baclofen significantly decreased mobility of rats (in the case of crossings to the level observed when AIDA was given alone), i.e. AIDA changed the effects of baclofen in the open field test. We also noted significant impairment of retrieval in rats pretreated with baclofen, which later received AIDA. AIDA significantly reduced the effect of baclofen on this memory process. In the elevated "plus" maze test, AIDA did not influence the behavior of rats pretreated with baclofen in comparison with the group treated with baclofen alone.

Animals↗

PubMedDate not supplied

NMDA receptor antagonists change behavioral activity of rats treated with (S)-4CPG.

The effect of (S)-4CPG [(S)-4-carboxyphenylglycine] (25, 50, 100 nmol icv) and the effect of AP-7 (5 nmol icv) or MK-801 (5 nmol icv) on the processes of acquisition, consolidation of conditioned reflexes and locomotor activity were tested in rats. Neither AP-7, MK-801 nor (S)-4CPG given alone changed locomotor activity. MK-801 significantly increased the effects of (S)-4CPG: on crossings at all applied doses, on rearings at 100 nmol, and on bar approaches at 50 nmol of (S)-4CPG. AP-7 enhanced the effects of 50 and 100 nmols of (S)-4CPG on crossings, 100 nmol of (S)-4CPG on rearings in the open field test. Neither AP-7, MK-801 nor (S)-4CPG at doses of 50 and 100 nmols influenced acquisition, but (S)-4CPG given alone at a dose of 25 nmol impaired acquisition. MK-801 impaired the action of 50 and 100 nmols of (S)-4CPG on acquisition. AP-7 only at a dose of 100 nmol inhibited (S)-4CPG-induced acquisition. Neither AP-7, MK-801 nor (S)-4CPG given alone changed consolidation in passive avoidance situation while co-administration of AP-7 and (S)-4CPG at the doses of 50 and 100 nmols, affected this process. The obtained results support our hypothesis concerning the co-operation between group I mGluRs and NMDA receptors in some behavioral tests and the modulating effect of group I mGluRs antagonist on central action of NMDA receptor antagonists.

2-Amino-5-phosphonovalerate↗

PubMedDate not supplied

Relationship between the changes in the concentration of endoxan and the activity of kininforming enzymes within the Guérin tumor in rat.

The activity of rat kininforming system and endoxan level in certain organs and in the neoplastic tissue was studied. It was found that trypsin increases markedly the kininforming activity and endoxan level in the Guérin tumor, and slightly in the liver. A direct correlation between the level of endoxan when given with trypsin and the kinin activity were observed. The authors suppose that the selective accumulation of endoxan in the tumor depends on the trypsin -- induced activation of kininforming system within the neoplastic tissue.

Animals↗