Modification of pentobarbital effects by natural and synthetic polypeptides: Dissociation of brain and pituirary effects

Prange, Arthur J.; Breese, George R.; Jahnke, Gloria D.; Martin, Billy R.; Cooper, Barrett R.; Cott, Jerry M.; Wilson, Ian C.; Alltop, Lacoe B.; Lipton, Morris A.; Bissette, Garth; Nemeroff, Charles B.; Loosen, Peter T.

doi:10.1016/0024-3205(75)90300-8

Cited by 68 publications

(4 citation statements)

References 18 publications

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“…If the decreased 125 i_Tyrll -somatostatin binding found following PTZ kindling is a reflection of a functional subsensitivity, then the present data lend support to the view that a decrease in response to somatostatin, a central nervous system depressing neurotransmiter (46)(47)(48), may be a general mechanism involved in the development of increased seizure susceptibility.…”

Section: Discussionsupporting

confidence: 77%

Cysteamine normalizes cerebral somatostatin level and binding in pentylenetetrazol-kindled rats

et al. 1989

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SummaryRats were kindled by intraperitoneal injection of pentylenetetrazol (PTZ) (30 mg/Kg) every 48 h. Once kindled, some of the animals received a single injection of cysteamine (200 mg/Kg). Somatostatin-like immunoreactivity (SLI) and 125 I-Tyr II -somatostatin binding were measured in the frontoparietal cortex and hippocampus of the two experimental groups and the control rats. After PTZ kindling the following was observed: i) SLI content was increased in the two areas; 2) Somatostatin receptor affinity decreased in the frontoparietal cortex and was unaltered in the hippocampus;3) The number of somatostatin receptors decreased in the hippocampus and was unaltered in the frontoparietal cortex. Cysteamine, an agent which depletes brain somatostatin and suppresses kindled seizures in PTZ-treated rats, reversed the altered SLI levels and binding in these rats."Kindling" refers to an experimental model of epilepsy in which repeated administration of a subconvulsive dose of a drug (pentylenetetrazol, cocaine, carbachol and lidocaine) or electrical current induces a progressive intensification of seizure activity, that culminates with a generalized seizure (1-6). Although the phenomenon of kindling has been extensively investigated, the basic biochemical mechanism underlyng the development and maintenance of this effect is still unclear.It has been suggested that the peptide somatostatin, a possible neurotransmitter or neuromodulator in the central nervous system (7), may play a role in kindling processes (8-11). It was recently reported that the levels of somatostatin-like immunoreactivity (SLI) are decreased in the rat brain, particularly in the striatum, by the injection of a single convulsant dose of pentylenetetrazol (PTZ) (12). Moreover, Assouline et al.(ll) have demonstrated that seizures in pentylenetetrazol-kindled rats are suppressed following systemic administration of cysteamine ( B -mercaptoethylamine), an agent which causes depletion of brain and gastrointestinal SLI (13). These results suggest that changes in endogenous brain SLI and/or receptors may be critically involved in the kindled state. To test this hypothesis, we used two approaches. First, we determined the effect of the repeated administration of subconvulsant doses of pentylenetetrazol on somatostatin levels and receptor number in rat frontoparietal cortex and hippocampus. Secound, the effect of cysteamine on the same parameters in rats which had been subjected to repetitive systemic administration of subconvulsive doses of pentylenetetrazol.

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Section: Discussionsupporting

confidence: 77%

Cysteamine normalizes cerebral somatostatin level and binding in pentylenetetrazol-kindled rats

et al. 1989

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“…TRH is a potent antagonist of barbiturate and ethanol-induced narcosis and hypothermia [5,35,36] and has also been reported to possess antidepressant properties [1,35] of TRH and a neurotropically active congener of the tri peptide (linear/(-alanine TRH; pGIu-His-Pro-/(-Ala-NH2), the possibility that some of the effects observed might be due to changes in thyroid status led us to examine the effects of chronic treatment with TRH or ft-ala TRH on serum concentrations of TSH, 1-triiodothyronine (T3) and thyroxine (T4). In some cases serum levels of growth hor mone (GH) were also studied.…”

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confidence: 99%

Effect of Chronic Treatment with Thyrotropin-Releasing Hormone (TRH) or an Analog of TRH (Linear <i>β</i>-Alanine TRH) on the Hypothalamic-Pituitary-Thyroid Axis

Nemeroff¹,

Bissette²,

Martin³

et al. 1980

Neuroendocrinology

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The effects of treatment for 5 or 9 days with varying doses of thyrotropin-releasing hormone (TRH) or the linear β-alanine TRH congener (pGlu-His-Pro-β-Ala-NH₂) on serum levels of TSH, T₃ and T₄ were studied in mice and rats. At low doses in rats treatment with TRH for 9 days significantly increased serum levels of T₃ but not serum T₄ whereas a higher dose of TRH (10 mg/kg) reduced serum T₃ levels. β-ALA TRH (0.1–10 mg/kg IP) treatment for 9 days in rats significantly reduced serum T₄ levels whereas serum T₃ levels were only depressed at higher doses (1–10 mg/kg IP) of the peptide. In mice treatment for 5 days with TRH (1 and 10 mg/kg IP) significantly reduced serum levels of T₃ and T₄. In addition, TRH (0.1–10 mg/kg IP) or β-ALA·TRH treatment (1.0–10 mg/kg IP) for 9 days significantly reduced serum TSH levels in rats. TRH (10 mg/kg IP for 9 days) also significantly reduced serum GH levels in rats. No alteration in hypothalamic content of TRH or LHRH was observed after chronic TRH treatment. Some, but not all, of our findings support the hypothesis that treatment with high doses of TRH reduce pituitary-thyroid axis functions by a direct effect on hypophysial TRH receptors.

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“…We have summarized the evidence for this viewpoint in another place (17). Salient among the evidence is the fact that certain congeners of TRH, for example /3-ALA TRH, are potent pentobarbital antagonists, but only weak thyrotropin releasers (3,16).…”

Section: Discussionmentioning

confidence: 99%

“…We have also reported that somatotropin release-inhibiting factor (SRIF, somatostatin) will extend pentobarbital effects to a significant degree while luteinizing hormone-releasing hormone, substance P, and L-prolyl-L-leucyl-L-glycinamide (often regarded as melanocyte-stimulating hormone release-inhibiting factor) are without effect (16). It thus became a matter of interest to study various parameters of pento barbital response as modified by the only two native polypeptides we have found capable of such modification, namely TRH and SRIF.…”

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confidence: 99%

Parameters of Alteration of Pentobarbital Response by Hypothalamic Polypeptides

Prange¹,

Breese²,

Jahnke³

et al. 1975

Neuropsychobiology

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Both thyrotropin-reieasing hormone (TRH) and amphetamine antagonize pentobarbital. They are more effective in the day than at night. This is true for TRH even when the dose of pentobarbital is increased at night to prolong sedation. Under this condition the day-night difference is lost for amphetamine. Both substances are more effective in cold ambient temperatures (18 °C) and less effective in warm temperatures, but their activity at warmer temperatures (37 °C) is still substantial. In contrast, somatotropin release-inhibiting factor (SRIF) augments the effects of pentobarbital at room temperature. This action is unaffected by time of day. However, the increase in sleeping time is lost in both a warm environment and in a cold environment.

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Modification of pentobarbital effects by natural and synthetic polypeptides: Dissociation of brain and pituirary effects

Cited by 68 publications

References 18 publications

Cysteamine normalizes cerebral somatostatin level and binding in pentylenetetrazol-kindled rats

Cysteamine normalizes cerebral somatostatin level and binding in pentylenetetrazol-kindled rats

Effect of Chronic Treatment with Thyrotropin-Releasing Hormone (TRH) or an Analog of TRH (Linear <i>β</i>-Alanine TRH) on the Hypothalamic-Pituitary-Thyroid Axis

Parameters of Alteration of Pentobarbital Response by Hypothalamic Polypeptides

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