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Biomedical subjects

K Hecht

Publications and source records attributed to K Hecht.

At least 55 records · Page 3Linked to original sources

Relation of substance P to stress and catecholamine metabolism.

Most research on substance P deals with its presumed function in the nervous system. Both excitatory and inhibitory actions have been observed in pharmacological studies. For example, substance P has a dual action on nociception in mice: it produces analgesia or hyperalgesia, depending on the dose and on the individual sensitivity to pain. This is interpreted to mean that substance P is capable of normalizing responsiveness to pain. Thus substance P could be classified as a regulatory peptide, or 'regulide'. A similar normalizing action of substance P was found in stress-induced disorders of sleep, behaviour and blood pressure in rats. The mechanism of this normalizing action is not yet clear. The decrease in activity observed for dopamine beta-hydroxylase and phenylethanolamine N-methyltransferase in adrenal glands of rats treated with the peptide may serve as a preliminary hypothesis.

Adrenal Glands

[Effect of substance P on dopamine-beta-hydroxylase and phenethanolamine-N-methyltransferase in the adrenal glands of rats].

Resulting from literature data concerning interactions between catecholamines and Substance P (SP) the influence of SP on the activity of dopamine-beta-hydroxylase (DBH) and phenylethanolamine-N-methyltransferase (PNMT) was studied in rat adrenals. Intraperitoneal application of SP (500 micrograms/kg) to male Wistar rats 15 minutes before decapitation induced a decrease of PNMT activity in the adrenals, while DBH activity remained unchanged. After incubation of adrenals with SP (10(-6) mol/l) a decrease of activity of both PNMT and DBH was observed. The experimental results are discussed in connection with a normalizing function of SP during stress induced disorders.

Adrenal Glands

Action of substance P and an SP-hexapeptide analogue on avoidance learning in rats.

The effects of Substance P (SP) (Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-MetNH2) and of a SP hexapeptide analogue (SP-A) (Lys-Phe-Ile-Gly-Leu-MetNH2) on active avoidance learning were investigated in spontaneously hypertensive rats (SHR) and Wistar rats. Active avoidance learning was slower in SHR than in Wistar rats. SP-A "normalized" the slower active avoidance learning in SHR, whereas SP did not. Some possible causes of this difference as well as the mechanism of the normalizing effect of SP-A are discussed.

Animals

[Asymmetrical distribution of noradrenaline in the neocortex, hippocampus and adrenal glands of rats and changes with chronic activity restriction].

The norepinephrine content of neocortex, hippocampus, and adrenals of adult male Wistar rats was estimated. In normal rats an asymmetrical right-left-distribution of the norepinephrine content was found. Neocortex and hippocampus showed a contralateral, neocortex and adrenals an ipsilateral ratio. Chronic stress cancelled this right-left asymmetry of norepinephrine distribution. In brain the levelling appeared earlier than in adrenals.

Adrenal Glands

Action of substance P and an analogue on blood pressure and avoidance learning in rats with spontaneous hypertension (SHR).

Substance P (SP) and an analogue (Lys-Phe-Ile-Gly-Leu-MetNH2 = EH) were tested in acute experiments on the blood pressure in the intact rat anaesthetized with urethane. A biphasic response, consisting of an initial depressor, followed by a pressor component, was seen. In low concentrations, SP decreases blood pressure, in medium concentrations SP produces a pronounced biphasic response, in high concentrations SP produces only hypertensive reactions. In chronic experiments, SP-peptides act also in different directions. After EH, disorders in avoidance learning were completely eliminated from 10 weeks old spontaneously hypertensive rats (SHR) or conditionally from SHR age 14 or 26 weeks. Elevated blood pressure in SHR aged 26 weeks was reduced by EH. Blood pressure in SHR aged 14 weeks was almost unaffected by EH and blood pressure went up in ten weeks old SHR. SP had a weaker action in comparison with EH. These results are in agreement with the hypothesis proposed by Oehme and co-workers [11-13] that SP can act as a regulatory peptide (="regulide").

Animals

Pyridostigmine administration in newborn rats prevents permanent mental ill-effects produced by maternal deprivation.

Maternal deprivation from Day 3 to Day 14 of life, i.e., separation of the pups from their mother animals during this developmental period for 16 hours each day, gave rise to highly significantly decreased learning capability and memory capacity in adulthood associated with significantly decreased acetylcholinesterase activity in the brain. These permanent ill-effects of the brain, produced by maternal deprivation of newborn rats, could be prevented by the acetylcholinesterase inhibitor pyridostigmine when administered from Day 1 to Day 14 of life. In view of these findings, teratogenic mental ill-effects, produced by psychosocial and/or nutritional deprivation during brain development, appear to be preventable by correcting abnormal neurotransmitter concentrations during this critical period of brain organization.

Acetylcholinesterase

Effects of neonatal pyridostigmine treatment on sexual maturation and adult behaviour in female rats subjected to maternal deprivation.

The present study deals with the effects on adult behaviour of early postnatal maternal, i.e. psychosocial and/or nutritional deprivation and of altering the brain levels and/or turnover rates of acetylcholine in preweaning deprived rats. The following data were obtained: 1. Female rats separated from their mothers and littermates for 16 hours each day during the first two weeks of life showed a significant delay of puberty onset in comparison with non-separated controls. Furthermore, these animals exhibited significantly reduced emotionality as well as learning capability and memory capacity in adulthood. 2. Administration of the acetylcholinesterase inhibitor pyridostigmine during the first two weeks of life to the deprived females did not compensate the puberty-delaying effect of separation. However, the neonatally pyridostigminized female rats exhibited an increased emotional reactivity in adult life. 3. Female rats deprived from their mothers and treated with pyridostigmine during the neonatal period displayed increased avoidance learning and memory capacity in adulthood as compared to neonatally deprived but untreated animals. It might be concluded from our results that defects of brain differentiation produced by early postnatal deprivation could be prevented, at least in part, by simultaneous administration of pyridostigmine.

Acoustic Stimulation

[Neuropeptides in regulation].

1. The thyroid gland is regulated on nerval and neurohormonal way by the hypothalamus, in which case the hypothalamus is regarded as one of the most important limbs in the chain of the limbic system. 2. The thyreotropin releasing hormone, a tripeptide, is characterized in its double function as releaser and as neuroregulator. As a releaser it controls the function of the thyroid gland by releasing the thyroid gland stimulating hormone of the pituitary gland and by guaranteeing the adaptation to various functional conditions through the thyroid hormones (T3 and T4). As a neuroregulator the thyroid gland stimulating hormone is able to stimulate irritation conditions, muscle tension, increase of temperature and the modification of the effect of neuropharmaca. Apart from this its antipsychotic and antidepressive effect is well-known. 3. The peptide character of such releasing hormones allows to conclude that these and their analoga may perform similar double functions. As instance for a neuroregulator investigations with substance P at the model of the neurotic hypertension and the spontaneous hypertension of the rat are cited and it is shown that this peptide or an SP-analogon may correct hyper- as well as hyporeactive changes in the regulation. Thus for the first time for substance P a universal normalising function could be demonstrated. 4. As a possible mechanism the principle of effectiveness of the probability and improbability relation is discussed and demonstrated in a simple model of representation.

Animals

[Behavior of thyroid hormones, corticosterone, adrenocorticotropic hormone and insulin in the plasma of the rat under stress conditions].

In male Wistar rats the behaviour of the plasma concentrations of thyroid hormones, corticosterone, adrenocorticotrophic hormone and insulin was examined in the course of a hypokinase stress of 6 weeks duration. Blood was taken after a stress of 1, 3 and 6 weeks. In these cases in thyroid hormones a decrease of the thyroxine (T4) and an increase of the triiodothyronine (T3) appeared. In an increased need of energy of the organism apparently a more rapid peripheral conversion of T4 to the more active metabolic T3 takes place. Only after a longer stress the deficit of thyroid hormone is equalized via the regulating circle hypothalamus-hypophysis-thyroid gland. The hormones ACTH and corticosterone which are connected together in the regulation system hypothalamus-hypophysis-adrenal cortex, after one week slightly increase in the plasma of rats and clearly decrease after a stress of 3 weeks. This shows that in a longer stress load apparently an exhaustion of the bioenergetic reserves of the organism develops. At last under long-term stress a significant decrease of the plasma insulin level was found. The decrease of insulin might be conditioned by an endogenic liberation of catecholamine.

Adrenocorticotropic Hormone

Substance P--new aspect to its modulatory function.

The paper deals with a modulatory function of Substance P (SP) (Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-MetNH2) with bearing on nociperception, behaviour, and norepinephrine uptake. The effect of SP on both nociperception and behaviour was found to depend on the original condition of the individuals. The individual response time of mice to thermic stimuli becomes standardized by Substance P in the hot-plate test. Disorders in acquisition of avoidance reactions caused by noiseborne stress were found to be fully normalized by SP, like certain vegetative parameters, such as blood pressure, heart rate, and respiratory rate. SP was found to inhibit or stimulate norepinephrine uptake of hypothalamus preparations depending on the experimental conditions. It is recommended to name peptides of the above type of action as "regulatory peptides" (regulides).

Acoustic Stimulation

[Edematous changes in the ultrastructure of the neocortex of Wistar rats following the application of angiotensin II].

In 80 Wistar rats were investigated the prolonged action of Angiotensin II in a dosage of 0,05 mg/kg/die ip. appl. on microstructures of the sensomotoric cortex. It is observed, after the first application, a biphasic reaction of brain vessels, in the beginning a pronounced vasodilatation (5 min p.-inject) which 10 min later turn into a vasoconstriction. In correlation with the applications frequency the repeated injection of the octapeptide leads to perivascular edemas. Neurons of the sensomotoric cortex show strong swellings, which later turn in to involutions. Pronounced destructions of mitochondria are demonstrable. Conceivable mechanisms were discussed.

Angiotensin II

[Experimental hydrocephalus using prolonged angiotensin II application].

In 80 wistar rats were investigated the prolonged action of Angiotensin II in a dosage of 0,05 mg/kg/die ip. appl. on macrostructures of brain. We tested the material 1-, 3-, 7-, 14- and 21 days after the first application. In correlation with duration of the Angiotensin II action a hydroencephalie was produced. This was marked by a lumen, so big as a 1/4-1/5 of the whole brain extent. Further we observed a considerable atrophy of brain structures, particularly in the corpus callosum and the white and gray Substance of cortex. Light-microscopically we would prove edemas perivasculary with separations of ependymal cells. Conceivable mechanisms were discussed.

Angiotensin II

Effects of a substance P-analogue on blood pressure and avoidance learning of rats with spontaneous hypertension.

A shortened and modified eledoisin-hexapeptide sequence (Lys-Phe-Ile-Gly-Leu-MetNH2) was tested for their action on avoidance learning and blood pressure of rats with spontaneous hypertension (SH-rats) and intact Wistar rats. Both groups were 10, 14, and 26 weeks of age. Disorders of avoidance learning and elevation of blood pressure were likely to aggravate along with growing age of SH-rat. The used eledoisin-hexapeptide sequence is related to the essential C-terminal pentapeptide sequence of Substance P (SP). After injection of the used hexapeptide at doses of 250 microgram/kg intraperitoneally disorders in avoidance learning were completely eliminated from ten-week SH-rats or conditionally for SH-rats aged 14 and 26 weeks. Elevated blood pressure in SH-rats aged 26 weeks was reduced by the hexapeptide from 220 Torr to approximately 190 Torr. Blood pressure in SH-rats aged 14 weeks, originally about 180 Torr, was almost unaffected by the hexapeptide. Blood pressure went up from about 150 Torr to 190 in ten-week-old Sh-rats. A hypothesis was made about the mode of action of Substance P and related peptides.

Animals

[Effect of a substance P analog on sleep deprivation].

The injection of 250 microgram/kg SP-analogue (Lys-Phe-Ile-Gly-Leu-MetNH2) is able to restore the reduced or disturbed delta activities and paradoxical sleep periods of the sleeping EEG in chronically stressed rats. Thus it has been proved that Substance P, which we would like to term as an ,,regulatory peptide" (equal to regulide) has a modulating function.

Animals