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Biomedical subjects

G Zetler

Publications and source records attributed to G Zetler.

At least 19 recordsLinked to original sources
PubMed1996

Effects of ceruletide and haloperidol on auditory evoked potentials in the cat brain.

The influence of cholecystokinin-like peptide, ceruletide, on EEG and auditory evoked potentials (AEPs) was studied in nine cats. The cats were bearing electrodes implanted in the auditory cortex, hippocampus, reticular formation and cerebellum. Reference drugs used were haloperidol and neostigmine. The hippocampus showed the strongest effect of ceruletide, whereas the cerebellum was virtually unresponsive. The amplitude of AEPs was increased by peptide, an effect lasting up to 21 days which, according to amplitude frequency analysis (AFC) was due to an augmented theta response. The latter possibly indicates increased signal transfer to, or through, the brain structure in question, particularly in the hippocampal neurons. The effects of haloperidol and neostigmine did not reflect those of ceruletide and lasted only a few hours.

Animals↗
PubMed1989

Noradrenergic, purinergic, and cholinergic transmission in the mouse vas deferens: influence of field-stimulation parameters, reserpinization, 6-hydroxydopamine and 4-aminopyridine.

In the field-stimulated mouse vas deferens the twitch inhibiting potency of prazosin (1 microM) and alpha,beta-methylene ATP (MeATP, 10 microM) was studied, using two types of stimulation-response curves, (a) variation of frequency from 3 to 100 Hz at a constant pulse width of 0.1 ms and (b) variation of pulse width from 0.04 to 0.8 ms at a constant frequency of 15 Hz. Prazosin and MeATP reduced the twitch response by eliminating the noradrenergic and purinergic component, respectively. After the combined application of both compounds a small third twitch component remained that was most prominent at high frequencies. Reserpinization reduced the effect of prazosin but enhanced that of MeATP and increased the cholinergic component. 6-Hydroxydopamine enhanced the effects of prazosin and MeATP to the same extent, but left the cholinergic component intact. In vasa pre-loaded with [3H]-noradrenaline, field stimulation induced a larger release of tritium at high frequency and short pulse duration (100 Hz, 0.1 ms) than at lower frequency and long pulse duration (15 Hz, 0.3 ms). Prazosin (1 microM) augmented both the spontaneous and the stimulation-induced overflow of tritium, whereas MeATP (10 microM) had only a negligible negative effect on the outflow of label. In conclusion, the twitch contraction of the mouse vas deferens has a small cholinergic component in addition to the noradrenergic and purinergic components. Adrenergic and purinergic transmission seem not to run strictly in parallel: the purinergic component dominates during stimulation at low frequency and long pulse duration, and after reserpinization; 4-aminopyridine enhances the adrenergic mechanism more than the purinergic one.

4-Aminopyridine↗
PubMed1989

The field-stimulated vas deferens of the streptozotocin-diabetic mouse: effects of prazosin, alpha, beta-methylene ATP, and variation of stimulation parameters.

The question of diabetic neuropathy was studied in the field-stimulated isolated vas deferens of the mouse. The animals were treated with either buffer or streptozotocin (170 mg/kg i.v.) 2 or 4 weeks, respectively, beforehand. Stimulus-response relationships were tested by variation of frequency (VF) at constant pulse width and by variation of pulse width (VP) at constant frequency. The adrenergic twitch component was eliminated by prazosin (1 microM) and the purinergic component by alpha, beta-methylene ATP (MeATP, 10 microM). The diabetes did not alter the muscular contractility (tested with KCl) and left the twitch-inhibiting effects of prazosin and MeATP unchanged, thereby revealing no difference in susceptibility between noradrenergic and purinergic mechanisms. However, in diabetic vasa, the maximal effectiveness of stimulation was decreased with VF but not VP, whereas the sensitivity of intramural neurons (50% effective frequency or pulse width, respectively) was unchanged with VF and reduced with VP. This may suggest that the diabetic neuron release less transmitter (VF), which can be compensated for by the activation of less sensitive neurons (VP). Actually, the uptake of 3H-noradrenaline into the (4 weeks-) diabetic vas was normal but the stimulation-induced fractional release of tritium was decreased by 26%. It is concluded that a sympathetic neuropathy occurred in the vas deferens of the streptozotocin-diabetic mouse.

Adenosine Triphosphate↗
PubMed1987

Cholecystokinin octapeptide, caerulein, substance P, neurotensin, and angiotensin II: species-typical effects on the isolated portal vein of guinea pig and rat.

The isolated, spontaneously active portal vein of guinea pig was stimulated by the following compounds (the pD2 is given in parentheses): caerulein (CER, 8.02), cholecystokinin octapeptide (CCK-8, 7.59), substance P (SP, 4.68), and carbachol (5.37), whereas neurotensin (NT) was ineffective and angiotensin II (AII) produced inhibition. On the portal vein of the rat, CER and CCK-8 were ineffective, whereas stimulation occurred with SP (5.72), NT (6.79), AII (7.89), and carbachol (5.50). Tetrodotoxin did not modify these effects in both types of preparation. Cyclic dibutyryl guanosine monophosphate reduced the effect of CCK-8 and CER but not that of carbachol. It is concluded that the peptides stimulate the portal vein in a way independent from intramural neurons. It may be speculated that receptors for CCK-8 and CER are absent in the portal vein of rat and those for NT in the guinea pig vein.

Angiotensin II↗
PubMed1986

Failure of coffee to inhibit the pharmacodynamic activity of morphine in vivo.

High doses of caffeine-containing as well as decaffeinated instant coffee neither inhibited morphine-induced analgesia in mice nor the morphine-induced fall of blood pressure, heart rate and respiratory rate in rats. On the contrary, caffeine-containing coffee even enhanced the analgesic effects of morphine in mice. Coffee thus does not exhibit opiate-antagonizing activity in the whole organism in vivo. The very weak morphine-antagonistic efficacy of coffee powder in the myenteric plexus-longitudinal muscle preparation from the guinea pig ileum is of no practical importance.

Analgesia↗
PubMed1986

Antistereotype effects of ceruletide and some neuroleptics differentiated by interactions with clonazepam, muscimol, scopolamine and clonidine.

Compulsive gnawing was produced in mice by administration of either methylphenidate or (after sensitizing pretreatment with the neuroleptic, tetflutixol) apomorphine. Drugs which antagonise stereotypy, such as ceruletide (CER, a sulphated decapeptide related to cholecystokinin octapeptide), haloperidol, zuclopenthixol and fluphenazine were applied in equipotent doses (reducing stereotypy by 80%). Clonazepam, muscimol, clonidine and scopolamine (but not methylscopolamine) antagonized to a different extent the antistereotype effect of ceruletide and the neuroleptics. The ED50s for clonazepam and other drugs, were determined; clonazepam had the greatest potency. Regarding the antagonism of the antistereotype effect, ceruletide was similar to but by no means congruent with haloperidol. The antagonism of the antistereotype effect was specific because other effects of ceruletide and cholecystokinin octapeptide (inhibition of exploratory rearing activity, ptosis, antinociception, hypothermia) were not antagonized by clonazepam and only weakly modified by scopolamine. Methylscopolamine was ineffective throughout, indicating a central site for the mechanism of the actions studied of scopolamine. In conclusion, the antistereotype effect of ceruletide is different from that of conventional neuroleptic drugs and functionally independent of other behavioural effects of the cholecystokinin-like peptides.

Animals↗
PubMed1985

Ceruletide inhibits water intake in deprived mice: comparison with morphine and the enkephalin analogue, FK 33-824.

Subcutaneous injections of ceruletide (caerulein diethylammonium hydrate, CER) reduced dose-dependently the water intake in male NMRI mice deprived of water for 18 h. The ED50 for this effect was 5.5 (3.70-7.94) nmol/kg, which is 3.7 times more than the corresponding food intake inhibiting dose. Also inhibitory but much less potent than CER were (in decreasing order) FK 33-824, morphine and naloxone. Naloxone was an antagonist to both FK 33-824 and morphine but not to CER, thereby separating CER from the opioids. When water intake reducing doses of CER (15 nmol/kg) and FK 33-824 (850 nmol/kg) were combined, the two peptides were not additive but antagonized each other. Together, the present and previous results suggest that pharmacological inhibition of food and water intake have different characteristics.

Animals↗
PubMed1985

Clonidine sensitizes mice for apomorphine-induced stereotypic gnawing: antagonism by neuroleptics and cholecystokinin-like peptides.

In mice sensitized for apomorphine by either scopolamine or teflutixol, clonidine antagonized the antistereotypic effect of ceruletide and haloperidol. The same effect of clonidine occurred in normal mice with methylphenidate-induced gnawing. In naive mice, clonidine alone had a sensitizing effect for the action of apomorphine leading to wire-gnawing. Yohimbine and rauwolscine (but not corynanthine) antagonized this effect of clonidine. The gnawing-inducing effect of methylphenidate was also enhanced by clonidine but not to the same extent as that of apomorphine. The stereotypic effect of apomorphine (in mice sensitized by either scopolamine or clonidine) was antagonized by yohimbine and rauwolscine but not by corynanthine. Apomorphine-induced wire gnawing was used as test of the antistereotypic effect of haloperidol, trifluoperazine, teflutixol, CCK-8, ceruletide and 8 related peptides. Ceruletide and 2 of its analogues were more potent than the neuroleptics; CCK-8 was 7 times less active than ceruletide. In conclusion, clonidine sensitized mice for the stereotypic effect (wire-gnawing) of apomorphine and methylphenidate. The clonidine-apomorphine effect permits the estimation of antistereotypic effects.

Animals↗
PubMed1985

Importance of frequency and pulse with in field stimulation of the mouse vas deferens: different behaviour of twitch-inhibiting drugs.

The effect of six twitch-inhibiting drugs on the stimulus-response relationship in the field-stimulated mouse vas deferens was compared by means of stimulus response curves which were obtained in two ways, that is, variation of frequency at constant pulse width and variation of pulse width at constant frequency. The twitch-inhibiting potency (in the range of maximal twitch responses) differed with the type of stimulation in a way permitting two groups of substances to be defined: group A (tetrodotoxin, procaine, verapamil) was more effective on frequency-response curves and group B (FK 33-824, clonidine, nifedipine) on pulse-width response curves; the latter applied also to subnormal calcium concentrations in the bath solution. The results suggest that the effect of inhibitory drugs on the field-stimulated vas of the mouse varies greatly with the type of field stimulation.

Animals↗
PubMed1985

Antistereotypic effects of cholecystokinin octapeptide (CCK-8), ceruletide and related peptides on apomorphine-induced gnawing in sensitized mice.

UNLABELLED: Cholecystokinin octapeptide (CCK-8), ceruletide (caerulein, CER) and 7 analogues of ceruletide, were studied for antagonism of stereotyped gnawing and cage climbing, induced by apomorphine in mice that were sensitized by either administration of scopolamine (1 mg/kg, s.c., 15 min before) or teflutixol (5 mg/kg, i.p., 4 days before). Three neuroleptics (haloperidol, trifluoperazine and teflutixol) served as reference drugs. All peptides reduced or abolished the fully developed gnawing activity and were (on a molar basis) often more potent than the reference drugs. In contrast to the neuroleptics, the peptides did not antagonize the climbing activity. In mice pretreated with scopolamine, the peptides were more potent than in mice pretreated with teflutixol. With the neuroleptics, the influence of the sensitizing pretreatments was converse, and this applied also to the anticlimbing effect. The relationships between peptide structure and antistereotypic effect were different from those found previously in a study on the antagonism of gnawing induced by methylphenidate. CONCLUSIONS: CCK-like peptides are able to antagonize stereotyped behaviour caused by direct and indirect dopaminergic agonists; the mechanism of action of the peptides differs from that of the reference neuroleptics.

Animals↗
PubMed1985

Caerulein and its analogues: neuropharmacological properties.

The decapeptide from the frog Hyla caerulea, caerulein (caerulein diethylammonium hydrate, ceruletide, CER) is chemically closely related to the C-terminal octapeptide of cholecystokinin (CCK-8). Like CCK-8, CER and some of its analogues produce many behavioural effects in mammals: inhibition of intake of food and water; antinociception; sedation; catalepsy; ptosis, antistereotypic, anticonvulsive and tremorolytic effects; inhibition of self-stimulation. Effects of CER in man comprise sedation, satiety, changes in mood, analgesia and antipsychotic effects. A modulation of central dopaminergic functions appears to be one possible mechanism of CER and its analogues. A common denominator for all effects of CER is, at present, not evident.

Animals↗
PubMed1985

Pharmacokinetics and effects of haloperidol in the isolated mouse.

The pharmacokinetic behaviour of haloperidol (0.6 mg/kg s.c.) was studied in grouped and 4-week isolated male mice of the CF-1 strain (24 h observation; gas chromatography, NPFID). Maximal drug levels occurred in serum within 2 min and in whole brain after 15 min. The elimination from serum and brain was biphasic with larger t1/2 values for brain. There was an accumulation of haloperidol in brain up to 40 times of the serum level. Isolation resulted in a more rapid first phase of elimination from serum, provided the animals were tested for aggressivity immediately before the administration of the drug. The minimal effective (i.e. cataleptogenic) brain level of haloperidol was approximately 0.1 microgram/g wet weight. Haloperidol-induced catalepsy was (after 1 h) in isolated mice weaker than in grouped mice; this applied to animals of both the CF-1 and the NMRI strain. The catalepsy disappeared after 6 h. The antagonism by haloperidol of the stereotyped gnawing (induced by methylphenidate, 30 and 50 mg/kg, i.p., NMRI mice) likewise lasted for 6 h. Therefore, the cataleptic effects, but not the brain levels of haloperidol, are influenced by isolation and aggression in mice.

Aggression↗
PubMed1984

Clonidine and yohimbine separate the sedation and the ptosis caused by cholecystokinin octapeptide and ceruletide.

The central depressant effects of ceruletide (CER, 0.04 mg/kg s.c.) and cholecystokinin octapeptide (CCK-8, 0.25 mg/kg s.c.) were compared with those of clonidine (0.04 mg/kg s.c.). At doses that were nearly equipotent with respect to motor inhibition (catalepsy, reduction in ambulation and exploratory rearing), only the peptides produced ptosis. Yohimbine (1 mg/kg s.c., 30 min) antagonized the effect of clonidine but not of the peptides. Clonidine (0.07-0.2 mg/kg s.c., 30 min) antagonised the ptotic action of the peptides, and this effect was abolished by yohimbine (0.2-1 mg/kg i.p.) but resistant to haloperidol (0.05 and 0.15 mg/kg i.p.). These results separate the behavioural effects of the peptides from those of clonidine and also the ptotic effect of the peptides from their effect on motor activity. The antiptotic effect of clonidine may originate from activated adrenergic autoreceptors.

Animals↗
PubMed1984

Effects of ceruletide and cholecystokinin octapeptide on eating in mice. Interactions with naloxone and the enkephalin analogue, FK 33-824.

Subcutaneous (SC) injections of ceruletide (caerulein diethylammonium hydrate, CER) and the octapeptide of cholecystokinin (CCK-8) reduced the intake of liquid food in male NMRI mice starved for 18 h. The corresponding ED50 values were 2 micrograms/kg for CER and 24 micrograms/kg for CCK-8; hence, on a molar basis, CER was 14 times more potent than CCK-8. Naloxone (0.2 and 1 mg/kg, SC) inhibited eating. (D-Ala)2(MePhe)4-(Met(O)-ol)5-enkephalin (FK 33-824; 0.3 and 1 mg/kg) was only stimulatory. Naloxone enhanced the effect of CER, whereas FK 33-824 antagonized it. It is concluded that concerning the inhibition of food intake, opioid peptides can be antagonists of CCK-like peptides. This is consistent with the current view of the regulation of appetitive behaviour.

Animals↗
PubMed1983

Neuroleptic-like effects of ceruletide and cholecystokinin octapeptide: interactions with apomorphine, methylphenidate and picrotoxin.

Haloperidol in low doses antagonized the apomorphine-induced cage-climbing behaviour of mice, whereas ceruletide (CER) and its analogue, Nle8-CER-(4-10) had very weak anticlimbing efficacy; Nle8-CER and diazepam were inactive. The ptosis caused by CER and cholecystokinin octapeptide (CCK-8) was antagonized by apomorphine in doses 27 times smaller than those effective against the haloperidol-induced ptosis. No such differences occurred when either methylphenidate or picrotoxin replaced apomorphine. Low-dose haloperidol was an antagonist to the antiptotic effect of apomorphine versus both CER and CCK-8. The rearing inhibiting effect of CER and haloperidol, in contrast to that of clonazepam, was very resistant to apomorphine. Methylphenidate was weakly effective against clonazepam and haloperidol but inactive versus CER. Picrotoxin was no antagonist to either rearing inhibiting agent. The results taken together suggest presynaptic sites of the dopaminergic system as important for the production of ptosis by CCK-like peptides.

Animals↗
PubMed1983

Apomorphine separates the antinociceptive effects of cholecystokinin octapeptide and ceruletide from those of morphine.

The antinociceptive effects of ceruletide (CER, 0.03 mg/kg s.c.), cholecystokinin octapeptide (CCK-8, 0.12 mg/kg s.c.) and morphine (0.33 mg/kg s.c.) were determined in mice with the hot plate test using paw licking and jumping up as endpoints. Licking was more resistant to antinociceptive effects than was jumping. Apomorphine 0.25 mg/kg, per se, produced more antinociception with licking than with jumping. With the jumping reaction, but not the licking response, apomorphine 0.063 and 0.125 mg/kg abolished the effect of morphine but did not modify that of CER and CCK-8.

Analgesics↗