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R Rips

Publications and source records attributed to R Rips.

36 records · Page 2Linked to original sources
PubMed1983

Enzymatic cleavage of pyroglutamyl-histidyl-dopamine, a TRH-related pseudo-peptide by porcine serum and brain hoimogenate.

The Pseudo-peptide (pGlu-His-Dopamine) was subjected to enzymatic degradation by porcine serum and brain homogenate. The digests were quantitatively analyzed by HPLC to provide evidence for liberation of pyroglutamic acid and dopamine in serum and of pyroglutamic acid in brain. The yield of liberation of pGlu is about 3% in serum digests and about 0.70% in brain digests after 3 minutes incubation. The time course of the yield of liberation of both pGlu and dopamine in serum digests is determined. The "stability in vitro" toward enzymes of serum and brain homogenate of a new type of drug based on the combination of peptidic fragment of TRH-(Thyrotropin-Releasing Hormone:pGlu-His-Pro-NH2) with a non peptide moiety (dopamine) is considered and discussed.

Animals↗
PubMed1983

Thyrotropin releasing hormone-induced hyperthermia in mice: possible involvement of adrenal and pituitary glands.

To investigate the hyperthermic effect of thyrotropin releasing hormone (TRH) and its potentiation by exogenous catecholamines (CA), the role of the adrenal medulla and of the pituitary gland was studied in unoperated, adrenal-demedullated or hypophysectomized mice. In unoperated mice, TRH 40 mg kg-1 i.p. produced a hyperthermia which was accompanied by an increase in plasma noradrenaline (NA) and adrenaline (Ad). NA or Ad, both at a dose of 1 mg kg-1 i.p., enhanced the TRH-induced hyperthermia. Adrenal demedullation suppressed the hyperthermia and the increase of plasma CA produced by TRH but not the potentiation of this hyperthermia by exogenous CA. Hypophysectomy abolished the TRH-induced hyperthermia but not the increase of plasma CA or the potentiation of this hyperthermia by exogenous CA. These results suggest that, in mice, both the adrenal medulla and the pituitary gland play an essential role in TRH-induced hyperthermia but not in its potentiation.

Adrenal Glands↗
PubMed1983

Antinociceptive properties of thyrotropin releasing hormone in mice: comparison with morphine.

1 To investigate the antinociceptive activity of thyrotropin releasing hormone (TRH) in mice, different nociceptive stimuli were used. TRH (i.p.) was active in the phenyl-p-benzoquinone or acetic acid-induced writhing tests (chemical stimuli) and in Haffner's test (mechanical stimulus); its action decreased rapidly 15 min after intraperitoneal injection. 2 To determine whether the activity of TRH has a peripheral or central origin, we administered TRH intracerebroventricularly via cannulae previously implanted in mice. The results provide evidence that a central mechanism is involved in the analgesic effect of TRH since when given intracerebroventricularly it was 10,000 and 1,000 times more active against chemical and mechanical stimuli respectively than intraperitoneally. The action of TRH decreased rapidly 5 min after i.c.v. injection. Morphine was studied in these tests and it was found that at the peak effect TRH analgesia (i.c.v.) was greater than that of morphine (i.c.v.) on a molar basis. 3 To investigate the mechanisms involved in the antinociceptive action of TRH, the effects of pretreatment with either agonists or antagonists of noradrenaline (NA), dopamine and 5-hydroxytryptamine (5-HT), or naloxone were studied. TRH activity was generally resistant to modifications of NA, dopamine and 5-HT systems. The TRH effect was not antagonized by naloxone, but TRH at a non-analgesic dose presented the hyperalgesia induced by naloxone. 4 In conclusion, TRH i.c.v. possessed a short, strong antinociceptive activity against chemical and mechanical stimuli. This analgesia was at least equipotent to that of morphine i.c.v.

Analgesics↗
PubMed1981

Effects of thyrotropin releasing hormone injections into different loci of rat brain on core temperature.

Intracerebral administration of thyrotropin releasing hormone (0.625--80 micrograms) induces moderate hyperthermia in Sprague--Dawley rats. The effect is more pronounced in the medical preoptic nucleus than in the lateral preoptic nucleus, n. accumbens, lateral ventricle and other regions. It lasts longer, however, in the n. accumbens. There is no effect in the stria terminalis. Hyperthermia is probably of central origin since intraperitoneal administration (20--80 mg/kg) under the same conditions has no clear effect.

Animals↗
PubMed1981

Implantation of an intracerebral cannula in the mouse.

A technique for implanting a permanent stainless steel cannula into the lateral ventricles of mice is described. The model is of particular interest because it permits study of the behavioral effects of acute or repeated administrations of substances in the brains of conscious mice. The method can be used for injection into parenchymal structures. A study of dexamphetamine effects on body temperature is presented to demonstrate the use of this technique.

Animals↗
PubMed1981

Conformational analysis of pGlu-His-Amph and pGlu-His-Pro-Amph related to their central nervous system activity.

The compounds pGlu-His-Pro-Amph and pGlu-His-Amph obtained from the condensation of TRH or a fragment of TRH with amphetamine show activities which are different regarding the parent compounds. Although the two derivatives exhibit about the same low toxicity they differ in several pharmacological properties. Physicochemical analysis by 1H-NMR and CD spectroscopy was carried out in order to detect in the two compounds conformational differences that might explain their different activities. The results show that in the proline containing peptide the amphetamine has a hindered rotation in comparison with the compounds devoid of proline. This, together with the occurrence of a cis conformer having different properties than the trans conformer could be the origin of the biological difference observed between the two hybrid compounds.

Amphetamine↗
PubMed1981

Evidence for the enzymic degradation of TRH-related pseudo-peptides by porcine serum and brain homogenate.

Pseudo-peptides (pGlu-His-amphetamine, pGlu-His-pro-Amphetamine and pGlu-amphetamine) were subjected to enzymatic degradation by porcine serum and brain homogenate. The enzymic digests were (qualitatively) analyzed by the "Finger-prints" technique to provide evidence for the presence of free pyroglutamic acid and also quantitatively by HPLC to provide evidence for the presence and yield of free amphetamine. The stability in vitro toward enzymes of serum and brain homogenate of a new type of drug based on the combination of a peptide moiety (TRH) with a non peptide psycho-tropic moiety (amphetamine) is also considered and discussed.

Amphetamines↗
PubMed1981

Use of potentiation of thyrotrophin releasing hormone (TRH)-induced hyperthermia as a test for screening antidepressants which activate alpha-adrenoceptor systems.

1 The minimal dose which significantly potentiates the hyperthermia induced by thyrotrophin releasing hormone (TRH, 40 mg/kg i.p.) in mice has been established for tricyclic and other antidepressants (imipramine, amitriptyline, clomipramine, nortriptyline, maprotiline, nomifensine, viloxazine) including a specific inhibitor of noradrenaline (NA) uptake (nisoxetine). 2 The minimal effective dose in this test has been compared with the minimal dose of the same compounds antagonizing reserpine-induced hypothermia. The ratio of the two doses for each substance indicates that potentiation of TRH-induced hyperthermia is, in general, the more sensitive test. 3 A correlation seems to exist between the alpha-adrenergic effect of antidepressants and the potentiation of TRH- induced hyperthermia. Those antidepressants which do not act on alpha-adrenergic systems (butriptyline, amineptine, trazodone, danitracen, fluoxetine) are inactive in this test. 4 This property may be used to select antidepressants that activate alpha-adrenoceptor systems.

Adrenergic alpha-Agonists↗
PubMed1980

Induction of wet-dog shakes by intracerebral 'acid' TRH in rats.

Less than Glu-His-Pro-OH or 'acid' TRH, until now considered to be an inactive metabolite of TRH, induces in rats when administered intracerebroventricularly (i.c.v.), stereotyped behavior and, from 12.5 micrograms, wet-dog shakes (WDS). WDS induced by 200 micrograms less than Glu-His-Pro-OH are antagonized by apomorphine, haloperidol and cyproheptadine while phentolamine and naloxone are without effect. For this action 'acid' TRH appears as effective as TRH itself and might have the same mechanism.

Animals↗
PubMed1980

Involvement of a central alpha-adrenoceptor system in antidepressant potentiation of hyperthermia induced by thyrotropin releasing hormone.

Thyrotropin releasing hormone (TRH) causes hyperthermia in mice which is potentiated by tricyclic antidepressants (nortriptyline, imipramine, clomipramine, amitriptyline), the monoamine oxidase inhibitor, tranylcypromine, and various other antidepressants (maprotiline, nomifensin, viloxazine). Only iprindole is ineffective. The effect of mianserin, itself hypothermic, could not be interpreted. A property shared by the potentiating substances seems to be activation of a central adrenoceptor system. The potentiation of TRH-induced hyperthermia which seems to be specific to antidepressants might be used in the selection of antidepressants.

Animals↗
PubMed1979

Is a dopaminergic system involved in thyrotropin releasing hormone induced hyperthermia and in its potentiation by amphetamine?

1. A dose-related hyperthermia is obtained in mice with TRH administered intraperitoneally. 2. This hyperthermia is reinforced by amphetamine given at doses which usually cause hypothermia. 3. p-Chloroamphetamine and L-Dopa also reinforce TRH hyperthermia. Apomorphine is not significantly active. 4. TRH hyperthermia is lowered significantly by alpha-methyl-tyrosine and haloperidol but not significantly by pimozide and chlorpromazine. TRH + Amph hyperthermia is not lowered by any of the DA antagonists tested even at doses reversing Amph hyperthermia. Direct participation of DA receptors is then doubtful. 5. All these variations of temperature have their acme a 15 min except for reserpine which, given 22 hours before, potentiates TRH + Amph hyperthermia after 30 min.

Amphetamine↗
PubMed1979

Evidence for the resistance of thyrotropin-releasing hormone (TRH) and pseudo-hormone, pyroglutamyl histidyl-amphetamine, to degradation by enzymes of the digestive tract in vitro.

TRH and pseudo-hormone (pyro Glu-His-amphetamine) were submitted to the digestion of chymotrypsin and prolidase and independently to the digestion of enzymes of the digestive track: pepsin (stomach), pancreatins (pancreas) and enzymes extracted from the intestinal mucosa (small intestine). Using thin layer chromatography and high voltage electrophoresis techniques to detect enzymic digestion products, only intact TRH and pseudo-hormone were found, indicating that both entities were, under the conditions used, resistant to in vitro digestion by enzymes of the digestive tract.

Amphetamines↗