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Biomedical subjects

B Penke

Publications and source records attributed to B Penke.

At least 91 records · Page 5Linked to original sources

The effects of atrial natriuretic peptide on electroconvulsive shock-induced amnesia in rats. Transmitter-mediated action.

Electroconvulsive shock (ECS) applied immediately after passive avoidance learning in rats caused partial amnesia. This could be prevented by administering r-ANP into the lateral brain ventricle. The effects of pre-treatment with different receptor blockers: (haloperidol, atropine, phenoxybenzamine, propranolol, naloxone, bicuculline and methysergide) on the ANP-induced antiamnesia were investigated. The receptor blockers per se in the doses selected had no influence on the ECS-induced amnesia. Haloperidol, atropine and propranolol blocked the antiamnestic action of the peptide, while phenoxybenzamine, naloxone, bicuculline and methysergide were ineffective. The results confirm our previous observations that ANP might play a role in learning and memory processes and also suggest that the antiamnestic action of the peptide is mediated by dopaminergic, cholinergic and beta-adrenergic mediator systems.

Amnesia↗

The effects of atrial natriuretic peptide on passive avoidance behaviour in rats.

The effects of rat atrial natriuretic peptide (ANP 1-28) on passive avoidance behaviour were tested following its administration into the lateral brain ventricle in rats. Different doses of ANP 1-28 were administered immediately after the learning trial of passive avoidance behaviour and the effects on the consolidation of learning were tested 24 h later. ANP 1-28, in doses in the range 50-2000 ng/rat, caused a dose-dependent increase in passive avoidance latency. Selected doses (100, 200 and 500 ng/animal) were given 30 min before the learning trial. These doses lengthened the passive avoidance latency in a dose-dependent manner. When the peptide was given 30 min before the retention trial, there was no significant alteration in passive avoidance response. The data suggest that ANP 1-28 is able to facilitate the learning and consolidation of fear-motivated passive avoidance behaviour.

Animals↗

Atrial natriuretic peptide assayed after immunoextraction with magnetic iron particles.

We investigated a new method for the immunoextraction of atrial natriuretic peptide (ANP) from plasma. Anti-ANP antibody was coupled to magnetizable iron particles by various coupling methods; both carboxyl terminal and amine terminal iron particles were examined. Introducing a chemical spacer between the iron particles and the antibody improved binding with ANP. The most efficient and reliable immunoextraction involves coupling the ANP antibody to amine terminal iron particles with bis-succinimidyl-suberate. Analytical recovery of ANP from this antibody-coupled suspension was 104% (SD 7.8%). We measured extracted samples by RIA. Standards were included in the extraction step. The detection limit of the assay was 3 ng/L. Patients' samples were assayed after both immunoextraction (y) and Sep-Pak C18 extraction (x); ANP values obtained with these methods correlated highly significantly y = 1.02x - 5.57 ng/L [r = 0.9302, n = 19, SE intercept = 5.7 (not significant), SE slope = 0.10 (P less than 0.0001)]. The method presented is potentially a reliable, efficacious immunoextraction method for ANP.

Atrial Natriuretic Factor↗

Somatostatin28(15-28), but not somatostatin28(1-12), affects central monoaminergic neurotransmission in rats.

The effects of intracerebroventricularly (icv) administered somatostatin28(SS28) fragments, SS28(1-12) and SS28(15-28), were investigated on central monoaminergic neurotransmission in rats. SS28(15-28) did not significantly influence the hypothalamic and striatal noradrenaline concentrations. In a dose-related manner, SS28(15-28) significantly increased the dopamine, dihydroxyphenyl acetic acid DOPAC), and serotonin concentrations in hypothalamus, but did not modify these measures in striatum. The other SS28 metabolite, SS28(1-12), had no statistically significant effects on the monoamine neurotransmission. SS28(15-28) (6 and 9 nmol) induced barrel rotation, while SS28(1-12) was ineffective following administration over a wide dose-range (3-18 nmol). In conclusion, SS28(15-28) influences the hypothalamic monoaminergic transmission and causes barrel rotation, whereas SS28(1-12) has no neurochemical or behavioural effects in these tests.

3,4-Dihydroxyphenylacetic Acid↗

Investigation of the influence of peptide-carrier conjugation on the immunological activity of VP1-peptides of foot-and-mouth disease virus O1-Kaufbeuren.

We found coupling of short sequences of VP1 to keyhole limpet hemocyanin (KLH) by means of glutaraldehyde to be a very complex phenomenon which could only be controlled by strict standardization of components and reaction conditions. Considering the results, we may conclude that big immunogenic proteins, like KLH, are advantageous for achieving sufficient and specific antibody response with neutralizing activity. When using KLH, we did not find simple dependence of immunogenicity or neutralizing activity on the incorporation rate of hapten in KLH in a region between 50 and 200. To develop a synthetic vaccine of good economy, investigations have to be continued, primary with a view to lowering the doses involved.

Animals↗

Protective effect of an orally administered, highly potent somatostatin analog (RC-121) against absolute ethanol-induced hemorrhagic erosions of the rat gastric mucosa.

The cytoprotective effect of a highly potent somatostatin (SRIF) analog, RC-121 (H-D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Thr-NH2), was examined in the absolute ethanol-induced gastric erosion model in rat. This analog diminished the degree of gastric erosion by 50-55% when administered in i.p. doses of 2 x 10(-10)-10(-8) g/100 g body weight, or in oral doses of 10(-8)-2 x 10(-7) g/100 body weight. The orally active, highly potent SRIF analogs may be useful as therapeutic agents in the treatment of human peptic ulcer.

Animals↗

The cytoprotective effect of the desamino-D-Trp 7-10 fragment of somatostatin on ethanol-induced erosions in the rat stomach.

The concept of cytoprotection was established by Robert. It means that several materials of different structure and in doses which are not antisecretoric ones, can protect the gastric mucosa against exogenous noxous agents. Absolute ethanol causes haemorrhagic erosions on the rat gastric mucosa. Somatostatin (SRIF) and its 7-10 fragment, which is the active centre of the hormone were cytoprotective in the ethanol-induced cytoprotective model. The desamino-D-Trp fragment (a suspected enzyme resistant variant of the active centre of SRIF) is also protective. It decreases significantly the extension of the lesions. Its dose-response curve shows two peaks, which may correspond to the existence of two SRIF receptor types, described in the rat gastric mucosa.

Animals↗

Effects of nocturnal intraperitoneal administration of cholecystokinin in rats: simultaneous increase in sleep, increase in EEG slow-wave activity, reduction of motor activity, suppression of eating, and decrease in brain temperature.

Rats received an i.p. injection of cholecystokinin-octapeptide sulfate ester (CCK; 4, 10 or 50 micrograms/kg) or physiological saline at dark onset, and the 24-h sleep-wake cycle (12-h-dark and 12-h-light phases), spontaneous motor activity and brain temperature (Tbr) were recorded. EEG activity was studied through spectral analysis for 2.5 h, and food intake was measured at the end of postinjection hour 1. In response to CCK, non-REM sleep increased at the expense of wakefulness, and the sleep-promoting effect was substantiated by an increase in EEG slow-wave activity. Motor activity, Tbr and food intake decreased. The effects vanished in postinjection hour 2; the diurnal rhythms were not modified. The changes varied as a function of the dose: the effects were significant following 10 micrograms/kg, and even higher in response to 50 micrograms/kg CCK. The results indicate that i.p. CCK definitely promotes non-REM sleep. This effect may belong to the behavioral sequence elicited by the peptide, which is often attributed to satiety. As evidenced by the reduction of Tbr, CCK also exerts strong autonomic actions, which might interfere with the behavioral responses.

Animals↗

Effects of cholecystokinin-related peptides on self-stimulation behaviour in rats.

The effects of cholecystokinin octapeptide sulfate ester (CCK-8-SE), its N-terminal tripeptide (CCK-2-4-SE) and its C-terminal tetrapeptide (CCK-5-8) were investigated on hypothalamic self-stimulation in rats. CCK-8-SE and CCK-5-8 in 400 pmole doses inhibited self-stimulation behaviour, while CCK-2-4-SE was ineffective. In 80 pmole doses the peptides showed no effect. It is suggested that CCK-5-8 itself influences self-stimulation behaviour.

Animals↗

The effect of atrial natriuretic factor on arginine-8-vasopressin and oxytocin levels in various brain regions and plasma.

The effect of intracerebroventricular (i.c.v.) treatment of rat atrial natriuretic factor III (ANF III; 0.5 microgram) was measured on the arginine-8-vasopressin (AVP) and oxytocin (OXT) contents of rat hypothalamic and limbic brain areas as well as those in the plasma. The hormone concentrations were determined by radioimmunoassay (RIA). The administration of ANF III in conscious euhydrated rats resulted in a significant reduction of both AVP and OXT contents in the hippocampus. Ether anesthesia interfered with the effect of ANF III, since in anesthetized rats ANF III reduced the levels of AVP and OXT in the septal regions, too. ANF III had no effect on the basal plasma AVP and OXT concentrations, however, the peptide inhibited the plasma AVP and OXT elevation induced by hyperosmosis (intraperitoneal injection of 2.5% NaCl). The results suggest that ANF III may be important in the control of the activity of both the peripheral (hypothalamo-neurohypophyseal) and the central (brain) AVP-ergic and OXT-ergic systems.

Animals↗

Competitive mechanisms of basic peptides inducing transganglionic degenerative atrophy.

In addition to the classical microtubule inhibitors (antimitotic agents), transganglionic degenerative atrophy of central terminals of primary sensory neurons can be induced also by means of applying to a peripheral nerve basic polypeptides (Polymyxin B and Colimycin) and two basic derivatives of glutamic acid that do not exert any microtubule inhibition. This effect is independent of other pharmacological effects (histamine liberation, Ca2+ -binding, etc.) of the applied compounds, and probably it is based on a competitive reaction with nerve growth factor.

Animals↗

The effects of somatostatin and some of its tetrapeptide fragments on ethanol-induced gastric mucosal erosion in rat.

A study was made of the cytoprotective effects of somatostatin (SRIF) and its 3-6, 5-8, 7-10, 9-12 and 11-14 tetrapeptide fragments on absolute ethanol-induced haemorrhagic erosions in the stomach of rat. The SRIF molecule was found to prevent the gastric erosions induced by ethanol. The 7-10 and 11-14 fragments exhibited similar properties. There are two peaks in the cytoprotective dose-response curves. It is concluded that various fragments of SRIF can also exert cytoprotective effects.

Animals↗

High-performance liquid chromatographic detection of side reactions in peptide synthesis.

High-performance liquid chromatographic systems with chemically bonded packing materials were elaborated for monitoring synthetic stages during peptide coupling, purity control of peptides produced by solid-phase methods and detection of impurities formed as a consequence of side reactions such as oxidation, desulphation, racemization, transpeptidation, alkylation and decomposition. The technique was applied to the analysis of peptide hormones, neuropeptides, cyclopeptides, isopeptides and branched polypeptides based on poly-lysine. The mobile phases were methanol-acetonitrile-water mixtures containing phosphate, acetate, carbonate buffers or trifluoroacetic acid (pH 2-9). After optimization, baseline separations could be achieved for some critical peptide separations.

Alkylation↗

A new cytotoxin specific for the target cells of corticotropin-releasing factor.

To develop a cytotoxic agent selective for pituitary corticotropes, an analog of CRF, [Nle21,38,Arg36]rat (r) CRF, was conjugated to the plant toxin gelonin using glutaraldehyde as a cross-linking agent. In a two-step synthesis, glutaraldehyde was first coupled to the amino-terminal of the CRF analog. This was then reacted with gelonin to form a product, which contained 20 mol [Nle21,38,Arg36]rCRF/mol gelonin, as indicated by amino acid analysis. Efficacy and specificity of the gelonin-[Nle21,38,Arg36]rCRF conjugate were assessed in cultured rat anterior pituitary cells 3 days after a 12-h exposure to the cytotoxic conjugate, CRF, or gelonin. While pretreatment with the cytotoxic gelonin-[Nle21,38,Arg36]rCRF conjugate decreased cellular ACTH content by 74%, pretreatment with appropriate concentrations of CRF had no significant effect on cellular ACTH content. The ACTH secretory response to 2.5 nM CRF was completely eliminated by pretreatment with the gelonin-[Nle21,38,Arg36]rCRF conjugate; in contrast, pretreatment with identical doses of CRF had minimal effect. Neither pretreatment with CRF nor pretreatment with the gelonin-[Nle21,38,Arg36] rCRF conjugate had any effect on the content of LH or the LH secretory response to GnRH. These results indicate the efficacy and specificity of the conjugate of [Nle21,38,Arg36]rCRF to gelonin in eliminating CRF target cells.

Adrenocorticotropic Hormone↗

Inhibition of electroshock-induced seizures by cholecystokinin-related peptides in mice.

The effects of several doses of cholecystokinin octapeptide sulphate ester (CCK-8-SE) and nonsulphated cholecystokinin octapeptide (CCK-8-NS), and two CCK-related peptide analogues Ac-Thr5-caerulein, and nonsulphated Ac-Thr5-caerulein were investigated on electroshock-(ES)-induced seizures after intraperitoneal administration in mice. As parameters, the duration of the tonic and clonic phase of the fit, and those of postictal coma and behavioural depression were measured. CCK-8-SE decreased the duration of the clonic phase; its highest dose, 3.2 mumol/kg, shortened the coma. CCK-8-NS antagonized only slightly the clonic phase of seizure. Ac-Thr5-caerulein did not influence ES-induced seizures in any dose, only increased the duration of behavioural depression. Similarly to CCK-8-NS, the nonsulphated form of Ac-Thr5-caerulein inhibited selectively the clonic phase of seizures. The reference drugs, diazepam and phenobarbital, antagonized dose-dependently and most effectively the tonic phase of ES-induced seizures, but in much higher doses than did the CCK-related peptides. Besides, diazepam increased and phenobarbital decreased the duration of postictal coma. The results showed that the tested CCK-related peptides inhibit prevalently the clonic phase of ES-induced seizures after peripheral administration.

Animals↗