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Biomedical subjects

J D Fernstrom

Publications and source records attributed to J D Fernstrom.

At least 91 records · Page 5Linked to original sources
PubMed1981

The pineal does not concentrate arginine vasotocin from biological fluids in vivo.

The ability of the pineal gland to concentrate circulating arginine vasotocin (AVT) from biological fluids in vivo was examined in rats. Intraventricular and intracisternal injections of AVT failed to elevate net pineal AVT content, even though CSF AVT levels were greatly increased by these treatments. Intravenous injection of AVT did elicit a light increase in pineal AVT, but plasma peptide levels wee elevated enormously. Thus, it seems unlikely that an active uptake process for AVT functions in this gland.

Animals↗
PubMed1981

Dietary precursors and brain neurotransmitter formation.

The rates of synthesis of serotonin, acetylcholine, and, under certain circumstances, dopamine and norepinephrine by brain neurons depend considerably on the availability to brain of the respective dietary precursors. This precursor dependence seems to be related to the fact that the enzyme catalyzing the rate-limiting step in the synthetic pathway for each transmitter is unsaturated with substrate at normal brain concentrations. Moreover, brain levels of the individual precursors rise following oral or parenteral administration of the pure compound or the ingestion of certain foods. Precursor-induced increases in brain transmitter formation seem to influence a variety of brain functions and behaviors, which suggests that transmitter release has been enhanced. It now appears that these precursors may become useful as therapeutic agents for the treatment of selected disease states, wherein the disease is related to reduced release of transmitter. Examples of Parkinson's disease (tyrosine), myasthenia gravis (choline or phosphatidylcholine), depression (tyrosine), and possibly abnormal appetite (tryptophan). Perhaps the future will bring the identification of still other neurotransmitters, whose rates of synthesis depend on precursor availability. Two potential candidates for which some information is already available are glycine (a spinal cord transmitter) and the prostaglandins (some of which may function as neuromodulators or transmitters) (48, 49). Each time a new precursor-product relationship is described, an opportunity becomes available for determining whether the precursor might be useful in treating disease states related to reduced transmitter release by neurons. The opportunities are worth exploring, since the use of a natural dietary constituent, even in purified form, is likely to produce fewer unwanted side-effects than are seen following administration of synthetic drugs.

Acetylcholine↗
PubMed1981

L-Tryptophan injection enhances pulsatile growth hormone secretion in the rat.

The effect of injecting L-tryptophan or a serotonin receptor agonist [6-Cl-2-[1-piperazinyl]pyrazine ((MK0212)] on pulsatile GH secretion was studied in male rats bearing right atrial cannulae. After injection, blood samples were drawn at 15-min intervals for periods up to 4 h. L-Tryptophan administration (50 or 100 mg/kg, ip) significantly enhanced mean plasma GH levels measured over a 3.5-h period. Injection of another large neutral amino acid, L-valine (100 mg/kg, ip), did not influence plasma GH levels. However, when administered with tryptophan, valine blocked the tryptophan-induced enhancement of GH secretion and blunted the increases in brain tryptophan and serotonin levels that normally accompany tryptophan injection. Injection of MK-212 (2 mg/kg, ip) elicited an immediate rise in plasma GH levels; this effect was completely blocked by pretreatment with metergoline (2 mg/kg, ip), a serotonin receptor antagonist. Taken together, these data support the notion that treatments which increase serotonin receptor stimulation enhance or induce pulsatile GH secretion.

Animals↗
PubMed1981

Reduction in brain serotonin synthesis rate in streptozotocin-diabetic rats.

The rate of serotonin synthesis in brain was determined in streptozotocin-diabetic and normal rats using two methods. Both the rate of 5-hydroxytryptophan accumulation after aromatic amino acid decarboxylase inhibition, and the decline rate of 5-hydroxyindole acetic acid after pargyline treatment were significantly reduced in diabetic rats. The reduced rate of synthesis may be a direct result of significantly lowered brain tryptophan levels in diabetic rats.

Animals↗
PubMed1981

In vivo biosynthesis of L-[35S]Cys-arginine vasopressin, -oxytocin, and -somatostatin: rapid estimation using reversed phase high pressure liquid chromatography.

L[35S]Cys-arginine vasopressin, -oxytocin, and -somatostatin were purified from hypothalami and neurohypophyses 4 h after rats received L[35S]Cys via the third ventricle. After acetic acid extraction, Sephadex G-25 filtration, and chemoadsorption to C18-silica (Sep-Pak cartridges), the labeled peptides were rapidly separated by gradient elution, reversed phase, high pressure liquid chromatography (HPLC). The identity and isotopic purity of the labeled peptides were determined by several reversed phase HPLC procedures in conjunction with chemical modification. The labeled peptide fractions were at least 50% radiochemically pure. Using this HPLC isolation procedure, incorporation of L-[35S]Cys into each peptide was determined n hydrated and dehydrated rats. Label incorporation into arginine vasopressin and oxytocin in the hypothalamus and the neurohypophysis of dehydrated rats was 2-3 times greater than that in hydrated rats. Incorporation of label into hypothalamic and neurohypophyseal somatostatin was unaffected by the hydration state of the animal. This procedure thus provides a very rapid, but sensitive, set of techniques for studying the control of small peptide biosynthesis in the brain.

Animals↗
PubMed1981

Effects of precursors on brain neurotransmitter synthesis and brain functions.

This paper reviews factors which influence the levels of aminergic transmitters in the brain. In particular precursor availability to the brain influences the rates of synthesis of serotonin, the catecholamines, and acetylcholine by brain neurons. The diet readily influences brain neurotransmitter formation via this mechanism. At present, the importance of this relationship to body regulation is not well understood. Nonetheless, precursors (tryptophan, tyrosine, choline, and lecithin) have begun to find uses as therapeutic agents in the treatment of disease states involving diminished transmitter formation and release. Hopefully, these compounds will find a wide range of uses, as they lack many of the side effects that accompany the use of drugs.

Acetylcholine↗
PubMed1980

Administration of antisomatostatin serum to rats reverses the inhibition of pulsatile growth hormone secretion produced by injection of metergoline but not yohimbine.

We attempted to determine whether release of endogenous somatostatin (SS) in rats might mediate the apparent inhibition of growth hormone (GH) secretion produced by metergoline of yohimbine injection. Plasma GH levels in adult male rats bearing chronic right-atrial cannulae were measured at 15-min intervals during a 4-hour period around the onset of the daily dark period. Plasma GH levels in control rats (vehicle-injected) rose rapidly from low levels (< 10 ng/ml) just before darkness to very high levels (> 300 ng/ml) around the onset of the dark period, then declined to low values within 2 h. Injection of the serotonin receptor antagonist metergoline (5 mg/kg) or the adrenergic blocker yohimbine (10 mg/kg) 2.25 h before darkness significantly suppressed the subsequent rise in plasma GH levels. The effect of metergoline, but not yohimbine, on plasma GH was markedly reversed when animals were injected intravenously with anti-SS serum (0.5 ml) 1 h after drug administration. These data suggest that circulating SS may mediate the GH inhibition produced by injection of a serotonin receptor blocker; however, other factors are apparently involved in the suppression of GH secretion by yohimbine.

Animals↗
PubMed1980

Radioimmunologic detection and measurement of nonapeptides in the pineal gland.

RIAs have been developed for the nonapeptide hormones arginine vasotocin (AVT), arginine vasopressin (AVP), and oxytocin (OT). The AVP RIA can detect as little as 2 pg hormone and shows essentially no cross-reactivity with AVT or OT. The OT RIA is sensitive to 7 pg and shows no significant cross-reactivity with AVP or AVT. The AVT RIA is sensitive to about 5 pg; some cross-reactivity occurs with OT and AVP, but the RIA is suitable for assaying AVT levels in biological samples containing OT and/or AVP in concentrations up to 5 times greater than that of AVT. Using these RIAs, we found large amounts of AVT (up to 1.48 microgram/gland) in the chicken pituitary but no AVP or OT. The chicken pineal also contained AVT (about 300 pg/gland) and lacked AVP and OT. Bovine pineal glands appeared to contain all three peptides in roughly similar amounts (200-400 pg/gland). Pineal glands from a variety of rodents (including the rat) contained only very small amounts of AVT-like immunoreactivity (about 10 pg/gland) and no AVP or OT. Because AVT immunoreactivity appears in the pineals of several species, the peptide may subserve some physiological function of this organ. The functional roles, if any, of AVP and OT in the bovine pineal are unknown.

Animals↗
PubMed1980

Dietary protein intake influences the antihypertensive potency of methyldopa in spontaneously hypertensive rats.

When spontaneously hypertensive rats consumed a single meal before receiving methyldopa (MD), the increase in brain MD levels and the blood pressure reduction varied inversely with the meal's protein content. MD injection elicited a greater reduction in blood pressure (and a larger rise in brain MD) in spontaneously hypertensive rats consuming a protein-free meal than in fasting animals; it induced a smaller fall in blood pressure (and a smaller increase in brain MD) in spontaneously hypertensive rats ingesting a protein-containing meal than in fasting animals. This effect may depend on the large neutral amino acids contained in protein. Ingestion of a food identical in amino acid content to 18% casein, but containing an amino acid mixture instead of protein, also blunted the MD-induced fall in blood pressure. However, consumption of a similar diet, lacking the large neutral amino acids (but not other amino acids), elicited an MD-induced blood pressure reduction similar to that caused by ingesting a protein-free diet. The combined effects of meal consumption and MD injection on brain MD and blood pressure correlated significantly with the serum ration of MD to the sum of the natural large neutral amino acids and not with serum MD alone. Similar effects were also noted with chronic dietary and MD treatments. Thus, dietary protein content can influence significantly the potency of a clinically important amino acid drug that acts within the brain.

Amino Acids↗