Biomedical subjects

B Penke

Publications and source records attributed to B Penke.

At least 109 records · Page 6Linked to original sources

PubMed1986

Targeted immobilization of neurotransmitters and neuropeptides on agarose and on Acrylex polymers.

A new strategy was devised for the targeted immobilization of ligands on aminohexyl- and carboxyhexyl-agarose. Selectively protected neurotransmitter amino acids and neuropeptides were coupled to amino or carboxyl group-containing agarose derivatives using activated esters, mixed anhydrides or carbodiimides. After coupling, agarose beads were dehydrated and the protecting groups were cleaved in non-aqueous media with acids (trifluoroacetic acid, formic acid). Agarose beads were rehydrated and applied for affinity chromatography and cell surface recognition. The same compounds were coupled to derivatized polyacrylamide beads containing primary amino (Acrylex A), acyl hydrazide (Acrylex AH-100) or carboxyl (Acrylex C-100) groups. Protecting groups were removed by acidolytic cleavage. Oxytocin, vasopressin, tetra- and pentagastrin, cholecystokinin, leucine-enkephalin and carboxyl-bearing derivatives of the neurotransmitters noradrenaline, dopamine, histamine, serotonin, acetylcholine and gamma-aminobutyric acid were immunobilized on agarose and on derivatized polyacrylamide gels.

Acrylic Resins↗

PubMed1986

Structure-activity relationship in the effects of delta-sleep-inducing peptide (DSIP) on rat sleep.

DSIP and its analogues, [D-Trp1]-DSIP, [D-Tyr1]-DSIP, and [D-Trp1]-DSIP1-6, were injected ICV (7 nmol/kg) into rats at dark onset, and the sleep-wake activity was recorded during the 12-hr dark period and the subsequent 12-hr light period. The effects were evaluated with respect to baseline records obtained after artificial CSF injections. DSIP did not increase sleep, whereas both [D-Trp1]-DSIP and [D-Tyr1]-DSIP promoted sleep in the first part of the night. [D-Trp1]-DSIP1-6 had a prompt arousing effect. It is suggested that the sleep-promoting analogues act by facilitating slight endogenous sleep tendencies at some time after dark onset, while DSIP is degraded quickly and is therefore not effective. The increase of W after [D-Trp1]-DSIP1-6 may indicate that DSIP contains a fragment with an arousing effect. The results corroborate the notion that the active DSIP molecule has a pseudo-cyclic structure.

Animals↗

PubMed1986

Effect of oxytocin on acute enkephalin tolerance in mice.

Intracerebroventricular (i.c.v.) administration of a test dose of 0.5 microgram D-Met2-Pro5-enkephalinamide (ENK) resulted in analgesia. Acute tolerance developed if a tolerance-inducing high dose of 5 micrograms ENK was administered i.c.v. prior to the test dose. Tolerance appeared as a reduction of the analgesic effect of the test dose. Subcutaneous (s.c.) injection of oxytocin (OXT) inhibited the development of tolerance. It is suggested that OXT is able to modify the development of tolerance to enkephalins, which are ligands of delta-opiate rather than mu-opiate receptors.

Analgesia↗

PubMed1986

Somatostatin and (D-Trp8, D-Cys14)-somatostatin delay extinction and reverse electroconvulsive shock induced amnesia in rats.

In the present study the effects of somatostatin and its analogs on active avoidance behavior, electroconvulsive shock (ECS)-induced retrograde amnesia, and spatial-discrimination learning were compared in rats. (D-Trp8, D-Cys14)-somatostatin (as did the somatostatin molecule itself) delayed the extinction of active avoidance behavior, antagonized ECS-induced amnesia, and did not modify spatial-discrimination learning. Des-Asn5-(D-Trp8, D-Ser13) somatostatin and des-AA1,2,4,5,12,13,-(D-Trp8) somatostatin did not influence these behaviors. The data suggest that certain parts of the somatostatin molecule are important for its behavioral actions.

Amnesia↗

PubMed1986

Cholecystokinin-destroying activities of canine tissue homogenates.

We have studied the capacity of different canine tissue homogenates to destroy cholecystokinin in vitro. Tissues from the kidney cortex, lung, pancreas, and small bowel contained significant cholecystokinin-destroying activity. Only small amounts of activity were found in the liver, and no activity was detected in the kidney medulla, the gastric antrum, gallbladder, spleen, or in serum or plasma. The kidney cortex was the richest source of activity. The cholecystokinin-destroying enzyme isolated from the kidney cortex was heat-labile, non-dialyzable, and trypsin-resistant, with an optimum pH between 7 and 7.4. The enzyme was inhibited by chelating agents and by phenylalanine amide, although it was little affected by phenylalanine itself or proteinase inhibitors. The enzyme required divalent cation cofactors for its activity. After inhibition by EDTA, the enzyme could be reactivated completely with Mn2+, but not with Ca2+ or Mg2+ alone. The cholecystokinin-destroying enzyme was bound strongly to membranes, and during differental centrifugation, was sedimented with mitochondrial fractions of kidney cortex. The supernatant fraction of the solubilized enzyme obtained at 105,000 X g had a molecular weight of about 480,000 dalton. Since the enzyme could be inhibited by phenylalanine-amide, it would appear to act at the C-terminal end of the cholecystokinin molecule.

Animals↗

PubMed1985

Inhibition of haloperidol-induced catalepsy by cholecystokinin octapeptides after central administration to rats.

The possible cataleptogenic or anticataleptic effects of cholecystokinin octapeptide sulphate ester (CCK-8-SE) and desulphated CCK-8 (CCK-8-NS) were evaluated in rats after intracerebroventricular (i.c.v.) administration. Neither CCK-8-SE nor CCK-8-NS induced any sign of catalepsy. When haloperidol, in a dose of 1.0 mg/kg (i.p.), and either CCK-8-SE or CCK-8-NS, in doses of 8, 80 or 800 pmol (i.c.v.), were applied at the same time, the peptides significantly decreased the total duration of catalepsy, the 80 pmol dose being the most effective. For the inhibition of catalepsy CCK-8-NS was the more active as it decreased catalepsy scores even 120 min after administration. Both peptides showed only transient effects on the fully developed catalepsy induced by haloperidol.

Animals↗

PubMed1985

Depression of rat feeding in familiar and novel environment by sulfated and nonsulfated cholecystokinin octapeptide.

The effects of cholecystokinin octapeptide sulfate ester (CCK-8-SE) and nonsulfated cholecystokinin octapeptide (CCK-8-NS) were tested on feeding by rats in familiar and novel environment. In a familiar environment only intraperitoneally (IP) administered CCK-8-SE (0.8-24 nmole/kg) could inhibit 30 min food intake of 24 hr food-deprived rats, while the same doses of CCK-8-NS IP and both octapeptides (0.8-8000 pmole/rat) intracerebroventricularly (ICV) were totally ineffective. The effects of CCK-8-SE and CCK-8-NS on feeding were also tested in a novel environment, i.e., in an open field. The parameters of exploratory activity and food intake of 24-hr food-deprived rats were recorded simultaneously during a 15-min session. After IP injection, CCK-8-SE dose-dependently depressed the food intake, and the higher doses (8.0 or 24 nmole/kg) also decreased the open field parameters, including number of approaches to food. In the novel environment, 8.0 or 24 nmole/kg IP injected CCK-8-NS also depressed the food intake, whereas the incidence of grooming was enhanced after 8.0 nmole/kg CCK-8-NS. The most effective doses of both octapeptides increased the latency to first bite. For the open field test ICV treatment was also carried out with 8, 80 or 800 pmole doses of the octapeptides, and after 80 pmole CCK-8-SE ICV the food intake was decreased, and after 80 or 800 pmole CCK-8-SE and 800 pmole CCK-8-NS the food intake/approach parameter was depressed.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1985

Effects of intracerebroventricular injection of delta sleep-inducing peptide (DSIP) and an analogue on sleep and brain temperature in rats at night.

The effects of ICV injections of DSIP and omega-amino-caprilyl-DSIP (C-DSIP) on the sleep-wake activity and brain temperature (Tbr were studied in rats. The substances (7 nmol/kg) were injected at dark onset, and the sleep-wake activity and Tbr were recorded for 24 hr (dark and light periods, 12 hr each). Relative to the control recordings obtained after artificial CSF injection, the duration of sleep did not increase after either DSIP or C-DSIP. The only significant reaction was an increase of W 6 to 9 hr after the injection of either peptide. The course of Tbr after DSIP and C-DSIP was also identical to that recorded after the injection of artificial CSF. It seems that DSIP administered in a single ICV injection at dark onset does not promote sleep. The increase in W might be attributed to an indirect effect of DSIP or to a degradation product of the peptide.

Animals↗

PubMed1985

Cataleptogenic and anticataleptic activity produced by cholecystokinin octapeptides in mice.

The catalepsy induced by subcutaneously (sc.) and intracerebroventricularly (icv.) administered cholecystokinin octapeptide sulfate ester (CCK-8-SE) and desulfated cholecystokinin octapeptide (CCK-8-NS), and the effects of CCK-8-SE and CCK-8-NS on haloperidol-induced catalepsy, were investigated in mice. The results demonstrate the bimodal effect of CCK octapeptides in a catalepsy test. With sc. administration CCK-8-SE in the doses of 0.4 or 0.8 mumole/kg, but not CCK-8-NS at any dose, induced catalepsy. Furthermore, the catalepsy induced by CCK-8-SE was of short duration. With icv. administration only 40 pmole CCK-8-NS induced significant catalepsy. When 0.2, 0.4 and 0.8 mumole/kg sc. doses of CCK-8-NS or 0.4 pmole icv. dose of CCK-8-SE or CCK-8-NS was given in combination with intraperitoneal (ip.) administration of 1.0 mg/kg haloperidol, the total duration of catalepsy was suppressed. Finally, CCK-8-SE sc. when given in combination with haloperidol ip., exerted a biphasic, synergistic-antagonistic effect on the haloperidol-induced catalepsy.

Animals↗

PubMed1985

Cholecystokinin octapeptides influence tolerance to ethanol in mice.

The effects of graded doses of cholecystokinin octapeptide sulphate (CCK-8-S) and non-sulphated CCK-8 (CCK-8-NS) on the development of tolerance to the hypothermic effect of ethanol were investigated in mice. The animals were pretreated with daily doses of CCK-8-S, CCK-8-NS (0.003-30 nmol/animal s.c.) or vehicle, followed two hours later by the i.p. administration of ethanol (4 g/kg). The same treatments were repeated on three consecutive days. The hypothermic response to ethanol administration gradually diminished, this phenomenon being accepted as indicating the development of tolerance to ethanol. Both CCK-8-S and CCK-8-NS inhibited the development of tolerance. While CCK-8-S resulted in a linear dose-response effect (0.3-30 nmol/animal), CCK-8-NS gave rise to a bell-shaped curve with effective blocking doses of 0.3-3 nmol/animal. There was no difference in colonic temperature between peptide and vehicle-treated, ethanol-naive animals, indicating that the peptide did not change the initial sensitivity to ethanol.

Animals↗

PubMed1985

In vivo sulfation of cholecystokinin octapeptide. Possible interactions of the two forms of cholecystokinin with dopamine in the brain.

In most laboratories CCK-8(s) has been found to be the biologically active form of CCK-8 in the CNS. The role of CCK-8(ns) has scarcely been investigated and is poorly understood. CCK-8(s) exerts a transmitter and/or modulator role in this projection. CCK-8(ns), on the other hand, profoundly affects DA-ergic neurotransmission in the nigrostriatal DA-ergic projection. The octapeptide modulates the turnover and release of DA from this neuron population. DA-mediated behavioral reactions are also modulated by CCK-8(ns). We should emphasize that the biological importance of CCK-8(ns) in the CNS has hitherto generally been neglected. Our results point to the equivalence of CCK-8(s) and CCK-8(ns) in the CNS in most biological tests. In some cases the latter compound is the more potent one. In most of these tests the C-terminal fragment (tetragastrin = CCK-4) also proved to be active. It is most likely that a brain receptor population exists which can bind both forms of CCK-8 and even CCK-4. Nevertheless, the CNS could contain binding sites which bind only CCK-8(s) as a ligand. We have found that an unidentified sulfotransferase of the brain can sulfate CCK-8(ns) and thereby provide a ligand for the special receptors of CCK-8(s). It is likely that CCK modulates the turnover and release of DA, and vice versa. Theoretically, different biochemical mechanisms could exist for interactions between CCK octapeptides and DA. We have focused our investigations on the enzymic sulfation-desulfation processes of both CCK-8 and DA and have devised a hypothetical model for the possible interactions. Both CCK-8(ns) and DA could be sulfated in vivo, this enzymic reaction generally requiring active sulfate (PAPS). These two compounds could compete for the limited pool of PAPS, and thus CCK-8 and DA could mutually regulate their levels in the same cell by influencing one of the metabolic (DA) or synthetic (CCK-8(s)) pathways. CCK-8(s) also might provide the O-sulfate group for DA by enzymic transformation, and, conversely, DA-O-sulfate may sulfate CCK-8(ns) in a similar way. These trans-sulfation processes could also mutually determine the concentrations of DA and CCK-8 co-existing in one cell. Experiments to prove these models are planned.

Animals↗

PubMed1985

Antisera to gamma-aminobutyric acid. II. Immunocytochemical application to the central nervous system.

An antiserum to gamma-aminobutyric acid (GABA) was tested for the localization of GABAergic neurons in the central nervous system using the unlabeled antibody enzyme method under pre- and postembedding conditions. GABA immunostaining was compared with glutamate decarboxylase (GAD) immunoreactivity in the cerebellar cortex and in normal and colchicine-injected neocortex and hippocampus of cat. The types, distribution, and proportion of neurons and nerve terminals stained with either sera showed good agreement in all areas. Colchicine treatment had little effect on the density of GABA-immunoreactive cells but increased the number of GAD-positive cells to the level of GABA-positive neurons in normal tissue. GABA immunoreactivity was abolished by solid phase adsorption to GABA and it was attenuated by adsorption to beta-alanine or gamma-amino-beta-hydroxybutyric acid, but without selective loss of immunostaining. Reactivity was not affected by adsorption to glutamate, aspartate, taurine, glycine, cholecystokinin, or bovine serum albumin. The concentration (0.05-2.5%) of glutaraldehyde in the fixative was not critical. The antiserum allows the demonstration of immunoreactive GABA in neurons containing other neuroactive substances; cholecystokinin and GABA immunoreactivities have been shown in the same neurons of the hippocampus. In conclusion, antisera to GABA are good markers for the localization of GABAergic neuronal circuits.

Adsorption↗

PubMed1985

Antisera to gamma-aminobutyric acid. I. Production and characterization using a new model system.

Antisera to the amino acid gamma-aminobutyric acid (GABA) have been developed with the aim of immunohistochemical visualization of neurons that use it as a neurotransmitter. GABA bound to bovine serum albumin was the immunogen. The reactivities of the sera to GABA and a variety of structurally related compounds were tested by coupling these compounds to nitrocellulose paper activated with polylysine and glutaraldehyde and incubating the paper with the unlabeled antibody enzyme method, thus simulating immunohistochemistry of tissue sections. The antisera did not react with L-glutamate, L-aspartate, D-aspartate, glycine, taurine, L-glutamine, L-lysine, L-threonine, L-alanine, alpha-aminobutyrate, beta-aminobutyrate, putrescine, or delta-aminolevulinate. There was cross-reaction with gamma-amino-beta-hydroxybutyrate, 1-10%, and the homologues of GABA: beta-alanine, 1-10%, delta-aminovalerate, approximately 10%, and epsilon-amino-caproate, approximately 10%. The antisera reacted slightly with the dipeptide gamma-aminobutyrylleucine, but not carnosine or homocarnosine. Immunostaining of GABA was completely abolished by adsorption of the sera to GABA coupled to polyacrylamide beads by glutaraldehyde. The immunohistochemical model is simple, amino acids and peptides are bound in the same way as in aldehyde-fixed tissue and, in contrast to radioimmunoassay, it uses an immunohistochemical detection system. This method has enabled us to define the high specificity of anti-GABA sera and to use them in some novel ways. The model should prove useful in assessing the specificity of other antisera.

Adsorption↗

PubMed1984

The inhibition of tail-pinch-induced food intake by cholecystokinin octapeptides and their fragments.

The effects of intraperitoneally (ip.) and intracerebroventricularly (icv.) administered sulfated and nonsulfated cholecystokinin octapeptide (CCK-8-SE and CCK-8-NS) and their N- and C-terminal fragments on the tail-pinch-induced feeding behavior of rats were investigated. After ip. administration, only CCK-8-SE inhibited tail-pinch-induced food intake. After icv. administration, both CCK-8-SE and CCK-8-NS, in doses of 800 pmole/rat, reduced the amount of food eaten. Of the CCK fragments tested icv., the sulfated N-terminal fragments, the middle portion of the CCK-8-sequence (the CCK-3-6 fragment), and the C-terminal tetrapeptide depressed the food intake of rats during tail-pinch, whereas the C-terminal tripeptide significantly increased it. The results suggest that CCK peptides inhibit tail-pinch-induced feeding by separate mechanisms, depending on the route of administration.

Animals↗

PubMed1984

Further analysis of the effects of cholecystokinin octapeptides on avoidance behaviour in rats.

Experiments were performed to examine the acute effects of cholecystokinin octapeptides and fragments on the active and passive avoidance behaviour of rats following peripheral and central administration. Both the sulphated (CCK-8-SE) and non-sulphated cholecystokinin octapeptide (CCK-8-NS) and also the COOH-terminal tetra-, penta-, hexa- and heptapeptides of cholecystokinin octapeptide facilitated the extinction of active avoidance behaviour and retention of passive avoidance behaviour. This latter effect of cholecystokinin octapeptides was reversed by anxiolytic chlordiazepoxide pretreatment, showing that in these test situations cholecystokinin octapeptides are able to modify fear-motivation or arousal of the animals; their effect is at least partly similar to that of the neuroleptic substance haloperidol. Subcutaneous treatment with CCK-8-SE or CCK-8-NS appeared to be 3-10 times more effective than intraperitoneal treatment. Following intracerebroventricular administration, 100-300 times lower doses were needed to cause a behavioural effect similar to that after subcutaneous injection. Microinjection of CCK-8-SE or CCK-8-NS in the fmol dose range into the nucleus accumbens facilitated the extinction of active avoidance behaviour and attenuated the retention of passive avoidance behaviour, while microinjection of these peptides into the central amygdaloid nucleus caused opposite effects on these behavioural tests. It seems that the neuroleptic-like effects of cholecystokinin octapeptides are mediated through the nucleus accumbens, and the opposite action (non neuroleptic-like) through the central amygdaloid nucleus.

Amygdala↗

PubMed1984

Inhibition of seizures induced by picrotoxin and electroshock by cholecystokinin octapeptides and their fragments in rats after intracerebroventricular administration.

The anticonvulsive activity of cholecystokinin octapeptide sulphate ester (CCK-8-SE), non-sulphated cholecystokinin octapeptide (CCK-8-NS) and three different N- and C-terminal fragments were investigated against seizures induced by picrotoxin and electroshock in rats after intracerebroventricular administration. Doses of 0.8 and 80 pmol of CCK-8-SE and CCK-8-NS significantly enhanced the latency of seizures induced by picrotoxin and shortened the duration of the clonic phase of the seizures induced by electroshock. Only CCK-8-SE shortened the recovery time and only 0.8 pmol of CCK-8-SE could shorten the duration of the tonic phase of convulsions induced by electroshock. Doses of the octapeptides of 8000 pmol were ineffective, with the exception of CCK-8-NS in the picrotoxin test. Of the fragments tested, the C-terminal tetrapeptide, CCK-5-8, enhanced the latency of seizures induced by picrotoxin in a dose of 0.8 pmol, and had a dose-dependent biphasic effect on the duration of the clonic phase of seizures induced by electroshock. Intracerebroventricular administration of diazepam enhanced only the latency of tremor and clonic seizures induced with picrotoxin in a dose of 40 nmol. Twelve nmole of diazepam shortened the clonic phase of convulsions induced by electroshock. The peptides tested were much more active than diazepam, and their effective doses were comparable to the amounts of cholecystokinin octapeptide found in brain structures.

Animals↗

PubMed1984

The effects of sulfated and nonsulfated cholecystokinin octapeptides on electroconvulsive shock-induced retrograde amnesia after intracerebroventricular administration in rats.

The effects of several doses of intracerebroventricularly injected cholecystokinin octapeptide sulfate ester (CCK-8-SE) and nonsulfated scholecystokinin octapeptide (CCK-8-NS) were studied on electroconvulsive shock (ECS)-induced retrograde amnesia, as measured in a one-trial step-through passive avoidance paradigm. Both CCK-8-SE and CCK-8-NS were able to attenuate amnesia slightly when they were injected into rats 10 min prior to ECS treatment, possibly by reducing the severity of the ECS-induced seizures. Of the treatments carried out immediately after ECS, only the 0.8 pmole dose of CCK-8-NS could significantly restore retrograde amnesia. After treatment 20 min prior to testing 24-hr retention, no effect of the peptides was observed. The lack of a dose-dependency and of any effect on retrieval raises the possibility that the CCK octapeptides influence memory processes by an indirect mechanism.

Amnesia↗

PubMed1984

The effects of somatostatin, its fragments and an analog on electroconvulsive shock-induced amnesia in rats.

In the present study the effects of intracerebroventricularly [icv] administered somatostatin [linear and cyclic], somatostatin3-6, somatostatin7-10 and des AA1,2,4,5,12,13 [D-Trp8] somatostatin [ODT8-SS] were investigated on electroconvulsive shock [ECS]-induced retrograde amnesia in rats. The ECS significantly decreased the foot shock-induced avoidance latency, and thus caused retrograde amnesia. Somatostatin [linear and cyclic] in a dose of 0.6 nM had no action on the ECS-induced retrograde amnesia, while in doses of 3 nM and [cyclic only] 6 nM it significantly prevented it. Somatostatin3-6, somatostatin7-10 and ODT8-SS in doses of 0.6, 3 and 6 nM had no effect on the ECS-induced amnesia. These results indicate that the whole sequence of the original somatostatin molecule is needed to block the ECS-caused retrograde amnesia.

Amnesia↗