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Biomedical subjects

C Prasad

Publications and source records attributed to C Prasad.

At least 145 records · Page 8Linked to original sources

Increased phospholipid methylation in the myocardium of alcoholic rats.

Phospholipid methyltransferase activity is unevenly distributed throughout the contractile and the specialized regions of rat heart. Chronic alcohol treatment stimulated the incorporation of [3H-methyl]-methionine but not [3H-methyl]-choline into phosphatidylcholine by left ventricular slices. The increase in the incorporation of [3H-methyl]-group from [3H-methyl]-methionine into phosphatidylcholine was due to an increase in phospholipid methyltransferase activity.

Alcoholism↗

Developmental changes in the distribution of rat brain pyroglutamate aminopeptidase, a possible determinant of endogenous cyclo(His-Pro) concentrations.

The distribution of cyclo(His-Pro), thyrotropin-releasing hormone (TRH) and Pyroglutamate aminopeptidase activity in adult and developing rat brains were studied. A comparison of the subcellular distribution of Pyroglutamate aminopeptidase activity in hypothalamic and cerebral cortical extracts from adult rats exhibited remarkable differences. In hypothalamus, the enzyme activity was mainly associated with the soluble fraction whereas in cortex it was predominantly associated with the particulate fractions. During postnatal development, the brain concentrations of cyclo(His-Pro) and Pyroglutamate aminopeptidase activities declined with age. These data suggest that Pyroglutamate aminopeptidase activity, but not TRH, plays an active role in determining the levels of endogenous cyclo(His-Pro) concentrations in brain.

Aging↗

Cyclo (His-Pro): mapping hypothalamic sites for its hypothermic action.

Hypothalamic loci of Sprague-Dawley rats were individually injected with cyclo (His-Pro) to determine the sites where that metabolite of thyrotropin-releasing hormone acts to produce hypothermia. There was almost always a positive hypothermic response in the preoptic-anterior hypothalamic area (POA/AHA); injection into the posterior or middle hypothalamic areas or into the hippocampus caused no significant decrease in core temperature. The fact that only injection into the POA/AHA evoked hypothermia suggests that this area is a major hypothalamic site of action of cyclo (His-Pro) in modulating thermoregulation in the rat.

Animals↗

In vivo autoregulation of rat adenohypophyseal thyrotropin-releasing hormone receptor.

The possible mechanism of attenuation of thyrotropin response to exogenous thyrotropin-releasing hormone in vivo after repeated administrations of the releasing hormone has been studied. To this end, the effect of prolonged hormone treatment on the binding of hormone to its receptor in the anterior pituitary gland has been evaluated. The data show that prolonged hormonal treatment resulted in a reduction in the number (B max) but no the binding affinity (KD) of the receptor. The effect was reversible and depended on the duration of treatment. This phenomenon of down regulation or the decrease in the receptor number was found not to be due to either the metabolism of releasing hormone or its ability to activate pituitary-thyroid-axis.

Animals↗

Regional dissociation of histidyl--proline diketopiperazine (cyclo-(His--Pro)) and thyrotropin-releasing hormone (TRH) in the rat brain.

The concentration of cyclo-(His--Pro) and its precursor, thyrotropin-releasing hormone (TRH) were measured in seven different areas of rat brain using specific radioimmunoassays. Although the concentration of both of these peptides was highest in the hypothalamus, their distribution patterns in all other loci of the brain were dissimilar. These results suggest that factors in addition to TRH concentrations are important in determining the unique concentration pattern of cyclo-(His--Pro) in the brain.

Animals↗

Chronic alcohol consumption increases cyclo (His-Pro)-like immunoreactivity in the rat brain.

Administration of histidyl-proline diketopiperazine (cyclo (His-Pro)) to rats attenuates ethanol-induced sleep. To understand the role played by cyclo (His-Pro) in the pathophysiology of prolonged alcohol consumption, we have measured the distribution of this peptide in brains of control and alcohol-treated rats. The data show that prolonged alcohol consumption increases the concentration of cyclo (His-Pro) in hypothalamic as well as extrahypothalamic brain. These changes may reflect a physiologic adaptation of the brain during alcohol consumption.

Alcoholism↗

Thyrotropin-releasing hormone: its distribution and metabolism during development in bullfrog (Rana catesbeiana).

The development changes in the metabolism of thyrotropin-releasing hormone (TRH), cyclo (His-Pro) formation from TRH, and the levels of endogenous TRH in frog brain and skin were determined. The results indicated that TRH concentrations were considerably higher in brain than in skin, and in both of these structures TRH content increased significantly following metamorphosis to adulthood. This increase in TRH concentration is probably a reflection of a marked decrease in TRH-metabolism in adult frogs compared to tadpoles. However, the formation of cyclo (His-Pro) from TRH increased during the developmental period reaching to a maximum in adulthood. The possible role of cyclo (His-Pro) in the amphibian developmental process is discussed in relation to our recent observation showing cyclo (His-Pro) inhibition of prolactin secretion.

Animals↗

The postnatal development of the pituitary thyrotropin-releasing hormone receptor in male and female rats.

The density of the pituitary TRH receptor in male and female rats was measured during postnatal development. The younger rats of both sexes exhibited higher [3H]TRH binding than did adults. A comparison of the properties of receptor binding between 4-5 day-old and adult pituitary showed that the increased binding was solely due to an increase in Bmax (maximum binding capacity) and not the KD (binding affinity). In conclusion, these findings demonstrate that the increased TRH-receptor density may be a contributing factor in eliciting exaggerated TSH response to exogenous TRH in neonatal rats.

Animals↗

Synthesis of phosphatidylcholine from phosphatidylethanolamine by at least two methyltransferases in rat pituitary extracts.

Rat pituitary extracts contain at least two methyltransferases that methylate phosphatidylethanolamine to phosphatidylcholine using S-adenosylmethionine as the methyl donor. The first enzyme methylates phosphatidylethanolamine to phosphatidyl-N-monomethylethanolamine and has a high Km (40-42 microM) for S-adenosylmethionine, whereas the second enzyme(s) catalyzes two successive methylations of phosphatidyl-N-monomethylethanolamine to phosphatidyl-N,N-dimethylethanolamine and then to phosphatidylcholine and has a low Km (6.7 microM) for S-adenyl-L-methionine. The first enzyme is loosely bound to the membrane fraction; therefore it appears in both particulate (20,000 X g) and supernatant (20,000 X g) fractions, whereas the second enzyme(s) is tightly bound to the membrane and thus appears only in the particulate fraction. Both methyltransferases have two pH optima of 6.5 and 9.5 (9.5 activity greater than 6.5 activity) and they do not require Mg2+.

Animals↗

Histidyl-proline diketopiperazine decreases food intake in rats.

Histidyl-proline diketopiperazine was found to suppress food intake during stress-induced eating (10(-6)--10(-8) mol), starvation-induced eating (10(-8) mol) and over an 8 h period of spontaneous eating (10(-8) mol). In contrast, other cyclic piperazines failed to alter food ingestion. The suppressive effect of histidyl-proline diketopiperazine was antagonized by the enkephalin analogue, D-Ala-Met-enkephalin, in equimolar concentrations.

Animals↗

TRH and histidyl-proline diketopiperazine inhibit cholesterol synthesis in dog intestine.

Low concentrations of thyrotropin-releasing hormone and one of its metabolites, histidyl-proline diketopiperazine, are shown to have an inhibitory effect on the activation of 3-hydroxy-3-methylglutaryl coenzyme A reductase which occurs during organ culture of canine intestinal mucosa. Somatostatin and vasoactive intestinal polypeptide, in contrast, are shown to have no effect. Thyrotropin-releasing hormone, recently shown to be present in gut mucosa, may be a physiological regulator of intestinal cholesterol synthesis. Histidyl-proline diketopiperazine, an active metabolite of the hormone, is possibly the active agent since its inhibitory effect was observed at a concentration as low as 10(-12) M. These observations demonstrate an effect on intestinal metabolism by a neurotransmitter-like hormone at potentially physiologic concentrations.

Animals↗

Protein deprivation and the brain: effect on enzymes and free amino acids related to glutamate metabolism in rats.

6-week-old, female albino rats were fed one of three diets containing 5, 10 and 20% casein for a period of 15 days. Rats fed the low protein diet (5% casein) lost weight (6.3 +/- 0.7 g/week), whereas those on the two higher protein diets gained weight. The concentrations of protein and free amino nitrogen in the brain were significantly lower in those on the low protein diet (5% casein) compared to those on the high protein diet (20% casein). The activities of brain enzymes, glutamine synthetase, glutamine transferase, glutaminase I, glutaminase II and glutamate decarboxylase, and the concentrations of free amino acids, aspartic acid, glutamic acid, glutamine, alanine and GABA were also lower. The prospect for nutritional rehabilitation of rats fed the low protein diet appeared to be excellent and was illustrated by the reversal of the above changes after 15 days on the high protein diet. The diet containing 10% casein was sufficient for the normal production of enzymes and free amino acids related to glutamate metabolism.

Amino Acids↗