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Biomedical subjects

B Penke

Publications and source records attributed to B Penke.

At least 145 records · Page 8Linked to original sources
PubMed1976

The structure of gastrointestinal hormones.

The primary and secondary structure of the three kinds of gastrointestinal hormones, i.e. gastrin, cholecystokinin-pancreozymin and secretin are discussed.

Amino Acid Sequence↗
PubMedDate not supplied

Membrane translocation of penetratin and its derivatives in different cell lines.

The third helix of the homeodomain of the Antennapedia homeoprotein can translocate through the cell membrane into the nucleus and can be used as an intracellular vehicle for the delivery of oligopeptides and oligonucleotides. A 16-amino acid-long peptide fragment, called penetratin, is internalized by the cells in a specific, non-receptor-mediated manner. For a better understanding of the mechanism of the transfer, penetratin and two analogs were synthesized:The conformation of penetratin peptides 1-3 was examined in both extracellular matrix-mimetic and membrane-mimetic environments. (1)H-NMR and CD spectroscopic measurements were performed in mixtures of TFE/water with different ratios. Peptides 1-3 were labeled by reacting their N-terminal free amino group with fluorescein isothiocyanate (FITC). Membrane translocation of the labelled peptides was studied with cell cultures [WEHI 164 murine fibrosarcoma cells (WC/1); chicken fibroblast cells (CEC-32); chicken monocytic cells (HD-11); human fibroblast (SV 80) and human monocytic cells (MonoMac-6)]. Confocal laser scanning microscopy and flow cytometry assay were used to study membrane translocation. Amphiphilicity was calculated for each peptide. In our experiments all the penetratin peptides penetrated into the cells. Helical conformation and membrane translocation ability showed little correlation: substitution of the two Trp with Phe increased the stability of helical conformation but decreased membrane translocation activity. The results of fluorescence microscopy and flow cytometry show that penetratin can be translocated into the cells by two mechanisms: endocytosis and direct transport through the cell membrane.

Animals↗
PubMedDate not supplied

Cholecystokinin-octapeptide-induced hypothermia in rats: dose-effect and structure-effect relationships, effect of ambient temperature, pharmacological interactions and tolerance.

Subcutaneous injection of cholecystokinin octapeptide (CCK-8) (0.005-1.25 mg/kg) elicited dose-dependent hypothermia in rats. The threshold of the response was between 0.01 and 0.05 mg/kg and the dose-response curve levelled off at doses larger than 0.2-0.5 mg/kg. Warm and cold ambient temperatures decreased and increased the response, respectively. Pretreatment with capsaicin, morphine, naloxone, atropine, haloperidol or propranolol did not affect the response to CCK-8, whereas pretreatment with phenoxybenzamine and a large dose of proglumide, an antagonist for CCK-receptors, attenuated the hypothermia. It seems that neither capsaicin-sensitive thermal and non-thermal afferents, nor opiate mechanisms are involved in the response, but alpha-adrenoceptors might be of some importance in the hypothermia. Non-sulphated-CCK-8, the C-terminal tetrapeptide and hexapeptide, [D-Ala4]-CCK-8 and [D-Met6]-CCK-8 were ineffective. Chronic treatment with CCK-8 resulted in the development of tolerance to the thermoregulatory effect, while the hypothermic responses to apomorphine and capsaicin were not affected. It seems that the tolerance cannot be attributed to conditioned homeostatic reactions.

Animals↗
PubMedDate not supplied

Inhibition of feeding by the C-terminal tetrapeptide fragment of cholecystokinin in a novel environment.

Several doses of the C-terminal tetrapeptide fragment of cholecystokinin octapeptide (CCK-5-8) were injected intraperitoneally (ip.) and intracerebroventricularly (icv.), and their effects on the feeding of 24-hr food-deprived rats in familiar and novel environments were studied. In the familiar environment, CCK-5-8 ip. or icv. had no effect on the food intake of the rats. In the novel environment (i.e. in an open field), CCK-5-8 showed merely slight effects on the main open-field parameters: only ip. administered CCK-5-8 enhanced the incidence of grooming. Of the feeding parameters tested in the open field, mainly the food intake/approach to food ratio was depressed by CCK-5-8 ip. or icv. The 24 mumole/kg ip. dose of CCK-5-8 decreased the food intake, while the 8 pmole icv. dose increased the number of approaches to food. After the treatments found to be the most effective, the latency to first bite was also enhanced. The results suggest that CCK-5-8 can amplify the arousal enhancement elicited by novelty through a central mechanism.

Animals↗
PubMedDate not supplied

Cholecystokinin interferes with the thermoregulatory effect of exogenous and endogenous opioids.

Intraperitoneal (ip) injection of cholecystokinin octapeptide sulfate ester (CCK; 5, 10 and 50 micrograms/kg) reduced the hypothermic response to 8 mg/kg and 32 mg/kg systemic morphine in restrained and freely moving rats, respectively. The hyperthermia elicited by a subcutaneous (sc) injection of 8 mg/kg morphine to freely moving rats was not diminished by CCK pretreatment. CCK (5 micrograms/kp ip) completely prevented the restraint stress-induced hyperthermia. Naloxone (1 mg/gk sc) was effective in antagonizing both the hyperthermic and the hypothermic effects of morphine and the stress-induced emotional hyperthermia. These results support the hypothesis that CCK may contribute to regulation of the endogenous opioid system.

Animals↗
PubMedDate not supplied

Multiple treatment potentiates the anticonvulsive activity of cholecystokinin octapeptides.

The dose-response curves for the anticonvulsive activity of sulfated and nonsulfated cholecystokinin octapeptide (CCK-8-SE and CCK-8-NS) against picrotoxin-induced (6 mg/kg SC) seizures were assessed either following or without pretreatment with a single high dose of CCK-8-SE or CCK-8-NS, to examine acute tolerance to the effect after IP injections in mice. As CCK-8-SE or CCK-8-NS pretreatment, a 1.6 mumole/kg dose was injected 2 hr prior to the second injection. No acute tolerance to the anticonvulsive activity was demonstrated, and CCK-8-NS pretreatment significantly potentiated its own anticonvulsive activity. Chronic (8-day) daily treatment with a 0.16 mumole/kg dose of CCK-8-SE or CCK-8-NS antagonized seizures by picrotoxin, presumably in a cumulative manner. To investigate the interactions of CCK octapeptides with other anticonvulsive agents, picrotoxin-induced seizures were antagonized with several doses of diazepam following or without acute, high-dose pretreatment with CCK-8-SE or CCK-8-NS. The two octapeptides only slightly modified the activity of diazepam: CCK-8-SE pretreatment displayed a tendency to antagonize it, while CCK-8-NS pretreatment to potentiate it. The results suggest that multiple treatment with CCK-8 induces sensitization of CCK receptors mediating anticonvulsive activity.

Animals↗
PubMedDate not supplied

Comparative studies of somatostatin-14 and some of its fragments on passive avoidance behavior, open field activity and on barrel rotation phenomenon in rats.

Behavioral effects of somatostatin-14, and some of its fragments [somatostatin(3-8), somatostatin(9-14), somatostatin(7-10)] after intracerebroventricular (ICV) administration have been investigated in male rats. In a passive avoidance learning test, somatostatin-14 (0.6 nM) given immediately after the learning session increased the avoidance latency at 24 hr after the injection, when compared to a somatostatin(3-8) (0.6 nM)-treated group. However, compared to a saline-treated group, the peptides did not significantly influence the avoidance latency. Somatostatin-14 administered in higher dose (6.0 nM) decreased the avoidance latency compared to the saline-treated group, while its fragments did not influence it. In an open field behavioral test, immediately after the 24-hr passive avoidance test, 6 nM of somatostatin-14 decreased the rearing activity, while the fragments did not influence this behavior. Somatostatin-14 produced barrel rotation in a dose-related manner, but after the injection of a high dose of the peptide (12 nM) all of the animals died in cardiorespiratory failure (apnea, pulmonary oedema). The fragments did not produce barrel rotation.

Amino Acid Sequence↗
PubMedDate not supplied

Effect of lysine-28 side-chain acetylation on the nanomechanical behavior of alzheimer amyloid beta25-35 fibrils.

Amyloid fibrils are self-associating filamentous structures formed from the 39- to 42-residue-long amyloid beta peptide (Abeta peptide). The deposition of Abeta fibrils is one of the most important factors in the pathogenesis of Alzheimer's disease. Abeta25-35 is a fibril-forming peptide that is thought to represent the biologically active, toxic form of the full-length Abeta peptide. We have recently shown that beta sheets can be mechanically unzipped from the fibril surface with constant forces in a reversible transition, and the unzipping forces differ in fibrils composed of different peptides. In the present work, we explored the effect of epsilon-amino acetylation of the Lys28 residue on the magnitude of the unzipping force of Abeta25-35 fibrils. Although the gross structure of the Lys28-acetylated (Abeta25-35_K28Ac) and wild-type Abeta25-35 (Abeta25-35wt) fibrils were similar, as revealed by atomic force microscopy, the fundamental unzipping forces were significantly lower for Abeta25-35_K28Ac (20 +/- 4 pN SD) than for Abeta25-35wt (42 +/- 9 pN SD). Simulations based on a simple two-state model suggest that the decreased unzipping forces, caused most likely by steric constraints, are likely due to a destabilized zippered state of the fibril.

Acetylation↗
PubMedDate not supplied

Haloperidol attenuates beta-amyloid-induced calcium imbalance in human fibroblasts.

BACKGROUND: Antipsychotics are widely used in the treatment of behavioral and psychological symptoms of dementia. A low frequency of Alzheimer's disease in patients with schizophrenia is reported, and it has been proposed that antipsychotic medications, such as haloperidol, may be responsible. Disruption of intracellular calcium levels is considered to play a key role in beta-amyloid-induced neurotoxicity in Alzheimer's disease. Haloperidol has also been reported to interact with calcium homeostasis through dopamine-2 and sigma-1 receptors, and other, yet unknown mechanisms. OBJECTIVE: Therefore, we investigated whether differences in the basal intracellular free calcium levels of cultured cutaneous fibroblasts--cells that do not express dopamine-2 and sigma-1 receptors--derived from sporadic Alzheimer patients and from age-matched control individuals after haloperidol treatment might be present. METHODS: Intracellular calcium level was measured in Fura-2AM-loaded human fibroblasts by dual wavelength spectrofluorimetry. RESULTS: Alzheimer cells exhibited significantly lower calcium level as compared to the control cultures. Exposure of fibroblasts to beta-amyloid peptide resulted in increased calcium concentration of the control cells, but not of Alzheimer fibroblasts. Co-incubation of cultures with a therapeutic dose of haloperidol blocked the beta-amyloid-induced elevation of calcium. CONCLUSION: This finding indicates that haloperidol efficiently countervails ionic imbalance and suggests that it may serve as a potential agent in alleviating neurotoxic effects of beta-amyloid peptide.

Aged↗
PubMedDate not supplied

Solid-phase synthesis of porcine cholecystokinin-33 in a new resin via FMOC-strategy.

Porcine cholecystokinin-33 has been synthesized on solid phase and characterized both chemically and biologically. In order to develop a successful synthetic strategy, a new anchor molecule (4-succinylamido-2,2',4'-trimethoxybenzhydrylamine) was designed and coupled to aminomethyl-polystyrene. The resulting 4-succinylamido-2,2',4'-trimethoxybenzhydrylamine resin was successfully used for the synthesis of cholecystokinin-33 using N-fluorenylmethoxycarbonyl amino acid symmetric anhydrides. Tyrosine-O-sulfate has been synthesized by direct sulfation of tyrosine with chlorosulfonic acid and incorporated into the peptide sequence by coupling as N-fluorenylmethoxy-O-sulfatotyrosine-pentafluorophenyl ester. Side chains of the trifunctional amino acids were protected mostly by t-butyl-type protecting groups. The guanidino function of arginine was protected by the 2,2,5,7,8-pentamethylchromane-6-sulfonyl group. After completion of the synthesis, the peptide was cleaved off the support with 50% trifluoroacetic acid (15 min); this treatment cleaved the side-chain protecting groups simultaneously. Preparative high-performance liquid chromatography resulted in pure cholecystokinin-33 of full biological activity. The structure of the peptide was proved by amino acid analysis, IR and UR spectroscopy, fast atomic bombardment mass spectroscopy and comparative high-performance liquid chromatography of the synthetic and native cholecystokinin-33.

Amino Acid Sequence↗