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Biomedical subjects

B Penke

Publications and source records attributed to B Penke.

At least 127 records · Page 7Linked to original sources
PubMed1984

Comparative studies with somatostatin and cysteamine in different behavioral tests on rats.

In the present study the effects of somatostatin and cysteamine (a selective decreaser of the somatostatin level in the body) were compared in different behavioral tests on rats. Somatostatin inhibited the extinction of active avoidance behavior 8 hr and 24 hr after intracerebroventricular (ICV) treatment, while cysteamine facilitated it 4 hr and 8 hr after subcutaneous (SC) treatment. Somatostatin did not significantly influence the cysteamine-induced facilitation of the extinction. Somatostatin did not have a significant effect on T-maze spatial discrimination learning and reverse learning, whereas cysteamine markedly attenuated the performance 4 hr (1st day) after treatment. Somatostatin in a dose of 4 micrograms (ICV) increased the locomotor activity 10 min after treatment, while cysteamine markedly decreased all parameters of the open-field test. These effects of the drug had disappeared 24 hr after treatment. If different doses of somatostatin (4 micrograms or 10 micrograms ICV) were administered to cysteamine-pretreated rats, the peptide did not modify the drug-induced changes in the open-field test. The data suggest that the brain somatostatin might have a physiological role in the organization of certain types of behavior.

Animals↗
PubMed1984

Changes in brain monoamine levels of rats during cholecystokinin octapeptide-induced suppression of feeding.

Cholecystokinin octapeptide (CCK-8) in doses of 5 or 10 micrograms/kg was injected intraperitoneally to 24 hr food-deprived rats before a 30 min feeding period, and the dopamine (DA), norepinephrine (NE) and 5-hydroxytryptamine (5-HT) contents of the hypothalamus, mesencephalon, amygdala, hippocampus and striatum were measured thereafter. The experimental procedure (deprivation + food intake) alone could induce changes in the brain monoamine contents of saline-treated animals as compared to the nondeprived control group. The most striking effect was observed in the hypothalamus, in which the contents of all three monoamines decreased. In the deprived control group there was a significant positive correlation calculated by linear regression analysis between the amount of food eaten and the DA contents of the amygdala. Injection of CCK-8 before food intake testing decreased the DA contents of the hypothalamus. In the CCK-8-treated animals the correlation between food intake and amygdaloid DA contents disappeared. The CCK-8 treatment specifically gave rise to a significant positive correlation between the amount of food eaten and the NE content of the hypothalamus; such a relation could not be observed in the saline-treated group. The hypothalamic NE contents altered in parallel with the effectiveness of both doses of CCK-8 in inhibiting food intake. The results indicate the importance of the hypothalamic NE system in the food intake-suppressing effect of CCK-8.

Animals↗
PubMed1984

Synthesis of potent heptapeptide analogues of cholecystokinin.

Nine new analogues of acetyl-CCK-heptapeptide (Ac-Tyr(SO3H)2-Met3-Gly4-Trp5-Met6-Asp7-Phe8-NH2 ) were synthesized by solid-phase methodology. In a first series, the Asp7 residue was replaced by hydroxy amino acid sulfate esters. In another series, Gly4 was substituted by D-Ala, while Trp5 and Met6 were replaced by their D enantiomer. The introduction of the sulfate ester was performed with a new, mild, crystalline, and stable reagent, pyridinium acetyl sulfate. Each analogue that contained Tyr(SO3H)2 and a hydroxy amino acid sulfate ester [Ser(SO3H), Thr(SO3H), or Hyp(SO3H)] in position 7 proved to be more potent (1.9, 1.7, and 3.0 times, respectively) than CCK-8 in vitro (isolated gallbladder strips). While devoid of gastrin-like activity in vivo, these analogues had potent anticonvulsive activity. The analogues containing a D-amino acid residue were less potent than the parent compound in vitro. The D-Ala4 replacement, however, yielded a compound that was 40% as potent as CCK-8 in the in vitro test but showed prolonged duration of action on sphincter Oddi. While the 7-substituted Ac-CCK heptapeptides are among the most potent CCK analogues reported so far, the D-Ala4 replacement resulted, for the first time, in prolonged activity in vivo.

Amino Acid Sequence↗
PubMed1984

Effect of somatostatin and its fragments on turning behaviour induced by unilateral substantia nigra lesion in the rat.

The effect of somatostatin and its two tetrapeptide fragments was investigated on turning activity induced by unilateral substantia nigra lesion in rats. Somatostatin in a dose of 0.6 nM had no action on the turning behavior, while a dose of 6 nM increased slightly while a dose of 12 nM significantly the contralateral turning. Cys-Lys-Asn-Phe and Phe-Trp-Lys-Thr had no action in low or high doses on the turning activity of the animals. The results suggest that somatostatin has a direct postsynaptic dopamine receptor stimulating effect. It seems that for dopamine receptor stimulating action the complete somatostatin molecule is needed.

Amphetamines↗
PubMed1983

Structure-activity and dose-effect relationships of the antagonism of picrotoxin-induced seizures by cholecystokinin, fragments and analogues of cholecystokinin in mice.

Intraperitoneal administration of cholecystokinin octapeptide sulphate ester (CCK-8-SE) and nonsulphated cholecystokinin octapeptide (CCK-8-NS) enhanced the latency of seizures induced by picrotoxin in mice. Experiments with N- and C-terminal fragments revealed that the C-terminal tetrapeptide (CCK-5-8) was the active centre of the CCK octapeptide molecule. The analogues CCK-8-SE and CCK-8-NS (dose range 0.2-6.4 mumol/kg) and caerulein dose range 0.1-0.8 mumol/kg) showed bell-shaped dose-effect curves, with the greatest maximum inhibition for CCK-8-NS. The peptide CCK-5-8 had weak anticonvulsant activity in comparison to the octapeptides, 3.2 mumol/kg and larger doses of the reference drug, diazepam, totally prevented picrotoxin-induced seizures and mortality. The maximum effect of the peptides tested was less than that of diazepam. Experiments with analogues and derivatives of CCK-5-8 demonstrated that the effectiveness of the beta-alanyl derivatives of CCK-5-8 were enhanced and that they were equipotent with CCK-8-SE. Of the CCK-2-8 analogues, Ser(SO3H)7-Ac-CCK-2-8-SE and Thr(SO3H)7-Ac-CCK-2-8-SE and Hyp(SO3H)-Ac-CCK-2-8-SE were slightly more active than CCK-8-SE.

Animals↗
PubMed1982

Effects of cholecystokinin octapeptide sulphate ester and unsulphated cholecystokinin octapeptide on active avoidance behaviour in rats.

The effects of peripherally administered cholecystokinin octapeptide sulphate ester and its unsulphated form on the active avoidance behaviour of rats were studied. The acquisition of avoidance behaviour was impaired, while extinction was facilitated, following cholecystokinin octapeptide sulphate ester or unsulphated cholecystokinin octapeptide treatment. These peptides had no action on open-field activity. It is concluded that peripherally administered cholecystokinin octapeptide influences acquisition and extinction of active avoidance behaviour and this effect is unrelated to general motor activity of the animals.

Animals↗
PubMed1982

Effects of cholecystokinin-related peptides on retention of passive avoidance behaviour.

Effects of intraperitoneal administration of cholecystokinin (CCK)-related peptides were studied on retention of single-trial learning passive avoidance behaviour. The COOH-terminal octapeptide of CCK (CCK-1-8-SE), the unsulfated octapeptide (CCK-1-8-NS), as well as the COOH-terminal tetrapeptide of CCK (CCK-5-8), administered immediately after the learning trial, facilitated passive avoidance behaviour. The data indicate that these peptides may influence memory consolidation processes.

Animals↗
PubMed1981

Serotonin-immunoreactive cells in the superior cervical ganglion of the rat. Evidence for the existence of separate serotonin- and catecholamine-containing small ganglionic cells.

Superior cervical ganglia of 8 adult male rats were examined by indirect immunofluorescence microscopy, using an antibody to a conjugate of bovine serum albumin and serotonin, and an antibody to a conjugate of bovine serum albumin and noradrenaline. The fixative used was 4% paraformaldehyde in 0.1 M phosphate buffer, pH 7.3. Consecutive cryostat sections of whole ganglia were alternately stained with these antibodies. Serotonin- as well as catecholamine-immunoreactive, small ganglionic cells were demonstrated, both arranged in clusters. Serotonin-immunoreactive cells were mostly located at the cranial or caudal side of the ganglia. Serotonin-immunoreactive cells provided with processes were easily observed. Only a few mast cells were seen. Catecholamine-immunoreactive cells were rounded without processes. This cell type did not seem to have a preferential position within the ganglia. Intermingling of both immunoreactive, small ganglionic cells was not observed. A considerable variety in the number of both immunoreactive cell types was established. Catecholamine-immunoreactive cells were absent in 3 our of 8 animals. Evidence is provided that the catecholamine-immunoreactive cells are storing noradrenaline. The presented data seem to indicate the presence of 3 different types of small, intensely fluorescent (SIF) cells in the superior cervical ganglion of the rat, viz. a dopamine-storing, a noradrenaline-storing, and a serotonin-storing SIF cell type.

Animals↗
PubMed1981

Effects of cholecystokinin octapeptide on striatal dopamine metabolism and on apomorphine-induced stereotyped cage-climbing in mice.

The effects of sulfated (CCK-8-SE) and non-sulfated (CCK-8-NS) cholecystokinin octapeptide on striatal dopamine (DA) metabolism have been investigated on mice. CCK-8-NS facilitated the disappearance of striatal DA, measured after synthesis inhibition with 350 mg/kg of alpha-methyl-p-tyrosine. CCK-8-SE did not affect DA disappearance. In vitro uptake of [3H]DA by striatal slices was affected by neither CCK-8-SE, nor CCK-8-NS (10(-5) M). Potassium-induced in vitro release of [3H]DA from striatal slices was significantly increased by 10(-5) M CCK-8-NS: however, CCK-8-SE likewise increased DA release in this model system. Apomorphine-induced (1.0 mg/kg) stereotyped cage-climbing behavior was not affected by CCK-8-SE but was enhanced by CCK-8-NS. This effect could be antagonized by haloperidol, but not by naloxone. The data suggest that CCK-8-NS affects striatal DA release, disappearance and receptor sensitivity in the mouse. Dopaminergic mechanisms should therefore be regarded as a possible mode of action of CCK-8-NS on brain functions.

Animals↗
PubMed1981

Influence of cholecystokinin octapeptide sulfate ester on brain monoamine metabolism in rats.

The effects of intracerebroventricular administration of an 80 pmole dose of cholecystokinin octapeptide sulfate ester (CCK-8-SE) were tested on the dopamine (DA), norepinephrine (NE) and serotonin (5-HT) turnovers of the hypothalamus, mesencephalon, amygdala, septum, striatum and cerebral cortex in rats. CCK-8-SE in an 80 pmole dose decreased the DA turnovers of the hypothalamus, mesencephalon, amygdala and septum, while it increased that of the striatum. The NE turnovers were increased in the hypothalamus and amygdala, but decreased in the striatum. The 5-HT turnover decreased only in the hypothalamus.

Animals↗
PubMed1981

Effect of cholecystokinin octapeptide sulphate ester on brain monoamines in the rat.

The effect of different doses of intracerebro-ventricularly administered cholecystokinin octapeptide sulphate ester (CCK-8-SE) was studied on dopamine (DA), norepinephrine (NE) and serotonin (5-HT) contents in the hypothalamus, mesencephalon, amygdala, septum and striatum, 10, 20 and 60 min following administration. The DA and NE content increased and the 5-HT content decreased in the hypothalamus and mesencephalon. A biphasic action was observed in the amygdala of DA, NE and 5-HT depending upon the time and doses used. Similar action was seen on DA and NE in the septum. In the striatum, the DA and 5-HT content decreased while the NE level first increased and then decreased. The data indicate that the CCK-8-SE is able to modify the activity of DA, NE and 5-HT in different brain regions in a time and dose-dependent manner, with a local specific action.

Amygdala↗
PubMed1981

Effects of intraventricular administration of cholecystokinin octapeptide sulfate ester and unsulfated cholecystokinin octapeptide on active avoidance and conditioned feeding behaviour of rats.

The effects of cholecystokinin octapeptide sulfate ester (CCK-8-SE) and unsulfated cholecystokinin (CCK-8-NS) were studied following intraventricular administration on active avoidance and conditioned feeding behaviour of rats. In the CCK-8-NS and CCK-8-SE treated animals the acquisition of active avoidance and conditioned feeding behaviour were considerably impaired compared to the control; furthermore, these peptides caused a facilitated extinction of active avoidance and conditioned feeding behaviour. The data suggest that cholecystokinin octapeptide is capable of modifying the fear and hunger motivated behaviours of rats.

Animals↗
PubMed1980

Use of antibodies to norepinephrine and epinephrine in immunohistochemistry.

Antibodies were raised in rabbits and sheep with antigens prepared by coupling NE or E to bovine serum albumin. Tissues were fixed with either 4% paraformaldehyde or 4% paraformaldehyde plus 0.5% glutaraldehyde in 0.1 M sodium phosphate buffer (pH 7.3). Cryostat sections were stained by the indirect immunofluorescence technique. Two parenchymal cell types, representing the NE and E-storing cells, were observed in the adrenal medulla. In the central nervous system, fibers and perikarya could be visualized by the antiserum to the NE antigen. In the peripheral nervous system, NE immunoreactive fibers were demonstrated. There was no detectable cross reactivity of NE antibodies with regard to E and 5-HT. Cross reactivity of E antibodies to NE and 5-HT equally could not be demonstrated.

Animals↗
PubMed1979

Metabolism of C-terminal pentapeptide of gastrin in the rat. Part III. The catabolism of the BOC-pentapeptide and its distribution in the organs.

The metabolism of labelled BOC-14 C-glycine-pentapetide was investigated in rats, both in blood and urine. We report on the following findings: --radioactivity could be measured in the blood even after the disappearance of the bioactive- and immunoreactive pentapeptide. --the bulk of the radioactivity in the blood after 8 minutes originates from a metabolite which, after subsequent systematic chemical identification, proved to be the BOC-14C-glycine fragment of the pentapeptide. --the radioactivity in the urine comes entirely from this split product of the labelled pentapeptide --the organ distribution of radioactivity of labelled pentapeptide was checked after i.v. administration; 1 minute after the injection, most of the radioactivity was found in the liver, followed by the kidney, pancreas, jejunum and lung. After 1 hour, radioactivity could be detected only in the kidneys. It was concluded that the N-terminal amino-acid of the naturally occurring pentagastrin (glycine) remains linked to the BOC protecting group in the course of the catabolism of the molecule and this fragment is excreted in the urine.

Animals↗