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Biomedical subjects

M A Lipton

Publications and source records attributed to M A Lipton.

At least 37 records · Page 2Linked to original sources
PubMed1977

Neurotensin: central nervous system effects of a hypothalamic peptide.

The central administration of neurotensin, an endogenous hypothalamic tridecapeptide, produces a marked dose-related decrease in body temperature of mice and rats at an ambient temperature of 25 degrees C. This effect is even more pronounced when mice are placed at 4 degrees C to increase the rate of decline of body temperature. Other sequelae observed after central administration of neurotensin are decreases in locomotor activity in rats and a marked dose-related enhancement in pentobarbital-induced mortality, sedation and hypothermia. This latter effect was shown to be due to a significant reduction in the metabolic degradation of the barbiturate. None of the above-mentioned effects are observed after peripheral neurotensin administration, suggesting that this peptide does not readily cross the blood-brain barrier. Neurotensin appears to be one of a growing list of neuropeptides that can affect CNS function.

Animals↗
PubMed1977

Lack of effect of chronically administered thyrotropin-releasing hormone (TRH) on regional rat brain tyrosine hydroxylase activity.

Chronic treatment of adult male rats with TRH (1 or 10 mg/kg IP) for 5 or 9 days failed to alter the activity of tyrosine hydroxylase (TH), the enzyme regulating the rate-limiting step in catecholamine biosynthesis. In contrast, as previously described, chronic reserpine administration (0.5 mg/kg IP: 9 days) resulted in a significant rise in TH activity in midbrain, hypothalamus, pons-medulla and forebrain. These results suggest that the enhanced brain norepinephrine turnover reported to occur after treatment with TRH is not due to synthesis of new TH enzyme protein.

Animals↗
PubMed1976

Comparison of the analeptic potency of TRH, ACTH 4-10, LHRH, and related peptides.

Various peptide hormones appear to exert behavioral and pharmacologic effects apart from their classical endocrine actions. Thytrotopin-releasing hormone (TRH), for example, antagonizes the sedation and hypothermia produced by barbiturate and other depressant drugs and de Wied has shown that ACTH 4-10, TRH, LHRH and certain related substances show some activity in inhibition of extinction of a pole-jumping avoidance response in the rat. These data provided the impetus for screening ACTH 4-10, LHRH, and related peptides for analeptic activity. ACTH 4-10 and ACTH 4-7 were inactive in antagonizing pentobarbital whether administered peripherally or centrally. ACTH 4-7 amide and 4-Met(O2), 8-D-Lys,9-Phe-ACTH 4-9 were active regardless of route of administration LHRH and two tripeptide fragments (pGlu-His-Trp-NH, and pGlu-His-Phe-NH2) showed analeptic activity only after intracisternal administration. Thus, some peptide fragments related to ACTH 4-10 and LHRH were shown to share to some degree the analeptic properties previously demonstrated for TRH.

Adrenocorticotropic Hormone↗
PubMed1976

Age differentiation in depression: biochemical aspects.

No age is immune to depression but the elderly seem especially susceptible since the incidence and prevalence is highest in the age group 55-70. At all ages the causes of depression are multiple and not fully understood. Elderly people who have been prone to depression earlier in life are especially vulnerable to major life stresses but the incidence rises even among those who have not had depressions earlier in life. Evidence based largely upon the mechanism of action of drugs specifically therapeutic for depression suggests that depression is associated with alterations in the synthesis, storage, release, and utilization of chemical neurotransmitters. Enzymes involved in these mechanisms are under genetic control. Furthermore, alterations in the activity of these enzymes occur with aging. The interaction of these biological and psychosocial changes relates to increased depression in the elderly. Treatment with tricyclic antidepressants is usually effective but must be reinforced with appropriate environmental support systems.

Age Factors↗
PubMed1975

Parameters of alteration of pentobarbital response by hypothalamic polypeptides.

Both thyrotropin-releasing 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 degrees C) and less effective in warm temperatures, but their activity at warmer temperatures (37 degrees 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.

Amphetamine↗
PubMed1975

Effects of thyrotropin-releasing hormone (TRH) on the actions of pentobarbital and other centrally acting drugs.

Thyrotropin-releasing hormone (TRH) was found to antagonize pentobarbital-induced sleeping time and hypothermia. While 3 to 100 mg/kg of TRH reduced pentobarbital sleeping time when administered prior to the barbiturate, a dose-response relationship to TRH could not be established. However, doses of 10 to 100 mg/kg of TRH enhanced the lethality of pentobarbital when these compounds were administered simultaneously. Thyrotropin or L-triiodothyronine did not imitate and hypophysectomy did not reduce the effects of TRH, indicating that the pituitary is not essential for its antagonism of pentobarbital. Studies of TRH analogs provided further support of this view. In addition, TRH reduced the sleep and hypothermia produced by thiopental, amobarbital, secobarbital and phenobarbital, and it antagonized the hypothermia and reduced motor activity produced by chloral hydrate, reserpine, chlorpromazine and diazepam. Intracisternally administered TRH also reduced pentobarbital sleeping time and hypothermia, but melanocyte-stimulating hormone release-inhibiting factor and somatostatin administered by this route did not. While reduction of pentobarbital sleeping time by TRH could not be attributed to an affect on monoamine systems or to deamidated TRH, this action was reduced by intracisternally administered atropine, suggesting that cholinergic mechanisms may contribute to the effects of TRH. Thus, the results provide evidence that TRH acts on brain independent of an effect on the pituitary.

Animals↗
PubMed1975

Thyrotropin-releasing hormone (TRH) and its beta-alanine analogue: potentiation of the anticonvulsant potency of phenobarbital in mice.

Previous work has demonstrated that thyrotropin-releasing hormone (TRH) and its beta-alanine analogue (beta-ala TRH) are potent antagonists of barbiturate-induced sedation. This study sought to determine the effects of these oligopeptides on the anticonvulsant properties of phenobarbital in the maximal electroshock seizure (MES) test. Pro-leu-gly-NH2, another hypothalmic peptide was also examined. None of the peptides studied had any anticonvulsant properties of their own, but TRH and beta-ala TRH, though not pro-leu-gly-NH2, potentiated the anticonvulsant potency of phenobarbital. Thyrotropin (TSH) and tri-iodothyronine (T3) were in effective, suggesting that the effects observed with TRH are not mediated via the pituitary-thyroid axis. Since phenobarbital treatment of grand mal epilepsy is often limited by sedation and since TRH antogonizes sedation and enhances anticonvulsant effects of the barbiturate, the hormone or a congener may find value as an adjunct in therapy.

Animals↗