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Biomedical subjects

J H Jacoby

Publications and source records attributed to J H Jacoby.

At least 37 records · Page 2Linked to original sources
PubMed1979

Paradoxical short-term effects of cyproheptadine on insulin and glucagon release in the rat.

The administration of cyproheptadine (25 mg/kg; i.p.) resulted in an increase of plasma insulin and glucagon (measured using 30 K antibody) 30, 60 and 120 min after injection to fasted rats. This dose of cyproheptadine also induced a hyperglycemia whereas a lower dose (5 mg/kg; i.p.), which did not alter plasma hormone levels, was associated with a hypoglycemia. Fed rats showed a reduction of plasma insulin with a similar elevation of blood glucose after cyproheptadine. Administration of an exogenous load of arginine resulted in increases of plasma insulin and glucagon of a greater magnitude than induced by cyproheptadine, however, cyproheptadine pretreatment (25 mg/kg) completely suppressed the pancreatic response to the amino acid, resulting in blood hormone levels similar to values seen after cyproheptadine administered alone. Cyproheptadine pretreatment also prevented the hyperinsulinemia and hypoglucagonemia resulting from glucose loading. alpha-Adrenergic receptor blockade (with phentolamine), beta adrenergic receptor blockade (with propranolol) and adrenodemedullation did not alter pancreatic responsiveness to the drug.

Adrenal Medulla↗
PubMed1979

Studies on tryptophan accumulation in brain during methiothepin-induced enhancement of 5-hydroxyindole synthesis.

The elevation of brain tryptophan, 5-hydroxytryptophan and 5-hydroxyindoles (serotonin + 5-hydroxyindole acetic acid) that results from a tryptophan load is potentiated by prior administration of methiothepin, a serotonin receptor antagonist. Co-administration of valine with tryptophan attenuates these effects even in animals receiving methiothepin pretreatment. Administration of methiothepin and tryptophan to rats with widespread reduction of brain 5-hydroxyindole levels resulting from raphe lesions or 5,7-dihydroxytryptamine pretreatment still enabled brain tryptophan levels to rise considerably above the sum of increases found in animals receiving one or the other. Following transection of the spinal cord, the cranial portion still exhibited enhanced uptake of tryptophan and 5-hydroxyindole synthesis following methiothepin plus tryptophan treatment, however, both these events were absent in the caudal segment. Apparently, enhanced tryptophan uptake can proceed in the presence of minimal neuronal activity; however, when nerve impulse flow is eliminated, both 5-hydroxyindole synthesis and tryptophan uptake is impaired.

Amino Acids↗
PubMed1979

The acute effects of 5HTP, fluoxetine and quipazine on insulin and glucagon release in the intact rat.

5-hydroxytryptophan (5HTP), the immediate precursor of serotonin, induces a release of insulin and glucagon in the intact rat. These effects of 5HTP, which have previously been shown to be blocked by L-aromatic amino acid decarboxylase inhibition, were also prevented by methysergide (a serotonin receptor antagonist). Quipazine (a serotonin receptor agonist) did not alter pancreatic hormone release. Fluoxetine, a serotonin neuronal reuptake blocker did not effect insulin secretion and had a slight glucagon stimulatory effect, however the effects of 5HTP on insulin and glucagon release were not potentiated by fluoxetine pretreatment. Alpha and beta-adrenergic receptor blockade did not alter the pancreatic effects of 5HTP.

5-Hydroxytryptophan↗
PubMed1978

The acute pharmacologic effects of serotonin on the release of insulin and glucagon in the intact rat.

Serotonin (5HT) (5 mg/kg-25 mg/kg; i.p.) induced a dose-related increase of plasma glucagon (IRG) (using 30K antibody) 3 to 60 min after administration to overnight fasted rats. Blood glucose (BS) also increased as early as 10 min post-injection whereas plasma insulin (IRI) increased in a non dose-related (30 min to onset) manner. Adreno-demedullation prevented the rise of BS and IRI, but not IRG. Pretreatment with reserpine (5 mg/kg; i.p.; 24 hr earlier) did not prevent the actions of 5HT. Pretreatment with the alpha-adrenergic antagonist phentolamine (3 mg/kg-6 mg/kg; i.p.) reduced but did not prevent the subsequent rise of IRG, whereas beta-adrenergic blockade with propranolol (5 mg/kg-10 mg/kg; i.p.) was without effect. Phentolamine and the lower dose of propranolol (5 mg/kg) reduced the 5HT-induced hyperglycemia; whereas the higher dose (10 mg/kg) prevented the hyperglycemia. Phentolamine potentiated and propranolol prevented (5 mg/kg) or reversed (10 mg/kg) the 5HT-induced IRI rise. Pretreatment with the 5HT-antagonist, methysergide, prevented all the effects of 5HT. Precursor loading with 5HTP (5 mg/kg-50 mg/kg; i.p.) also resulted in a dose-related increase of IRG and a slight increase of IRI. Blockade of the conversion of 5HTP to 5HT with Ro-4-4602 (an L-aromatic acid decarboxylase inhibitor) blocked the subsequent rise of IRG. These results suggest that the 5HT-induced changes in BS and IRI may be secondary to a release of epinephrine and/or norepinephrine, but that the effects of 5HT on the release of IRG cannot be explained solely by this mechanism.

5-Hydroxytryptophan↗
PubMed1975

Failure of decreased serotonin uptake or monoamine oxidase inhibition to block the acceleration in brain 5-hydroxyindole synthesis that follows food consumption.

The acceleration in brain serotonin synthesis produced by injecting rats with tryptophan or allowing them to consume a carbohydrate diet was not blocked by the prior elevation of brain serotonin levels (by administration of a MAO inhibitor: Lilly 51641) or by a treatment (chlorimipramine administration) that decreases impulse flow along serotoninergic neurons.

Animals↗
PubMed1975

Altered growth of hormone secretory pattern following prolonged sleep deprivation in the rhesus monkey.

Plasma concentrations of growth hormone (GH) were determined in samples obtained sequentially at 15-min intervals during the last 4 h in monkeys deprived of sleep for 76 h and the first 8 h of ensuing recovery sleep. Electroencephalographic (EEG), electro-oculographic (EOG), and electromyographic (EMG) activities were recorded. Stages 3-4 sleep occurred rapidly after sleep onset and were of long duration. Plasma GH secretion was markedly elevated during sleep recovery, without apparent relationship to stage of sleep.

Animals↗
PubMed1975

Thyroid state and brain monoamine metabolism.

The rates at which rat brain synthesizes catecholamines and serotonin were estimated by measuring the accumulation of DOPA and 5-hydroxytryptophan (5-HTP) 45 min after ip administration of the decarboxylase inhibitor RO4-4602 (800 mg/kg BW). Following thyroparathy-roidectomy, hypothyroid rats showed a decreased accumulation of both precursor amino acids. On the other hand, hyperthyroidism (caused by administering 15 mug T4/100 g BW for 25 days) accelerated the accumulation of catecholamines and serotonin. The accumulation of 5-HTP correlated closely with brain tryptophan concentration in all treatment groups; DOPA accumulation, however, did not similarly correspond to brain tyrosine levels.

5-Hydroxytryptophan↗
PubMed1975

The mechanism by which methiothepin, a putative serotonin receptor antagonist, icnreses brain 5-hydroxyindole levels.

Brain tryptophan and 5-hydroxyindole levels are elevated in rats given methiothepin, a neuroleptic that appears to block serotonin receptors. The rise in brain tryptophan probably results from a drug-induced increase in the ratio of plasma tryptophan concentration to the sum of the neutral amino acids in plasma that compete with tryptophan for uptake into the brain; this change in the plasma amino acid pattern may be mediated in part by a methiothepin-induced rise in plasma insulin. Methiothepin also decreases the proportion of circulating tryptophan that is bound to albumin. Unlike exogenous tryptophan, methiothepin fails to increase 5-hydroxyin-doles caudal to the site of a spinal cord transection. Therefore, the mechanism by which methiothepin elevates 5-hydroxyindole levels involves not only increased brain tryptophan levels but also continued impulse flow along serotonergic neurons.

Amino Acids↗