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Biomedical subjects

G A Mason

Publications and source records attributed to G A Mason.

At least 73 records · Page 4Linked to original sources
PubMed1988

Chronic alcohol ingestion decreases pituitary-thyroid axis measures in Fischer-344 rats.

In a chronic feeding study adult male Fischer-344 rats (n = 12) were fed a nutritionally complete liquid diet containing 10% (w/v) ethanol for 40 days while control animals (n = 12) were pair fed a nutritionally complete isocaloric diet in which dextrose was substituted for ethanol. Treated animals were gradually introduced to and withdrawn from the 10% diet. At the end of the study and at sacrifice ethanol-fed rats had gained slightly more weight than pair-fed controls. They also showed a significant decrease in total thyroxine, free thyroxine, L-triiodothyronine, reverse L-triiodothyronine, and basal thyroid-stimulating hormone. These differences did not appear to result from caloric deprivation alone. Possible explanations for some of these thyroidal changes are discussed.

Alcoholism↗
PubMed1987

Dopamine receptors in human gastrointestinal mucosa.

Dopamine is a putative enteric neurotransmitter that has been implicated in exocrine secretory and motility functions of the gastrointestinal tract of several mammalian species including man. This study was designed to determine the presence of dopamine binding sites in human gastric and duodenal mucosa and to describe certain biochemical characteristics of these enteric receptor sites. The binding assay was performed in triplicate with tissue homogenates obtained from healthy volunteers of both sexes using 3H-dopamine as a ligand. The extent of nonspecific binding was determined in the presence of a 100-fold excess of unlabeled dopamine. Scatchard analysis performed with increasing concentrations of 3H-dopamine (20-500 nM) revealed a single class of saturable dopamine binding sites in gastric and duodenal mucosa. Binding parameters obtained from the regression lines of the Scatchard plots of gastric mucosa of males were Bmax = 73.4 +/- 4.0 pmoles/mg protein; KD = 154 +/- 20 nM and Bmax = 95 +/- 13.6 pmoles/mg protein and KD = 826 +/- 200 nM in females. In duodenal mucosa of males these parameters were Bmax = 63.9 +/- 15.9 pmoles/protein; KD = 235 +/- 53 nM and Bmax = 83.2 +/- 19.4 pmoles/mg protein; KD = 568 +/- 104 nM in females. The results of this report demonstrate the presence of specific dopamine receptors in human gastric and duodenal mucosa. These biochemical data suggest that molecular abnormalities of these receptor sites may be operative in the pathogenesis of important gastrointestinal disorders.(ABSTRACT TRUNCATED AT 250 WORDS)

Dopamine↗
PubMed1987

Effects of nonapeptide antagonists on oxytocin- and arginine-vasopressin-induced analgesia in mice.

Several peptides, including arginine-vasopressin (AVP), neurotensin, and substance P, produce analgesia that is not mediated by opiate systems. Using the hot plate test, we studied the analgesic effects of intracisternal (i.c.) administration of various doses of the nonapeptide oxytocin (OXY) in Swiss-Webster mice. We found that OXY (1-4 micrograms) significantly increased the latency of animals to jump or lick their paws after placement on a hot plate. This effect was not blocked by naloxone pretreatment, which suggests that it is not opiate dependent. Using the hot plate test, we confirmed that AVP (1 and 4 micrograms) also produces analgesia. We then studied the analgesia produced by OXY and by AVP using 3 nonapeptide analogues with antagonist properties: [Pen1, LpMePhe2, Thr4, Orn8]OXY (PLMPTO-OXY) that has anti-oxytocic properties in the uterine contraction assay, d(CH2)5Tyr(Me)AVP(dTM-AVP) which antagonizes the antidiuretic properties of AVP and d(CH2)5D-Ile2,Abu4-AVP (dIA-AVP) which antagonizes the vasopressor effects of AVP. Simultaneous administration of PLMPTO-OXY completely blocked the analgesia produced by OXY whereas the antidiuretic antagonist dIA-AVP partially blocked OXY-induced analgesia and dTM-AVP had no effect. None of the antagonists used blocked AVP-induced analgesia. We concluded that the neural systems mediating the analgesic effects of i.c. OXY differ from those for AVP.

Analgesia↗
PubMed1987

Effect of hypophysectomy, adrenalectomy, pituitary hormone secretion and gastric acid secretion on neurotensin induced gastric protection against stress gastric lesions.

In previous studies we have established that intracisternal (i.c.) but not peripheral (intravenous) administration of neurotensin (NT), a brain and gastrointestinal tridecapeptide, totally prevents the development of gastric lesions produced by cold-restraint stress (CRS) with food-deprived rats. In this investigation, removal of the pituitary and adrenal gland, anterior pituitary hormone secretion and gastric acid secretion were evaluated independently as potential intermediates for NT's protective effect. NT (30 micrograms) produced a significant reduction of gastric lesions incidence and severity in intact and sham-operated controls. Adrenalectomy, but not hypophysectomy totally blocked the protective effect of i.c. NT. In addition, replacement therapy with s.c. prednisone (1 mg/kg) for 5 days following adrenalectomy did not restore the protective activity of central (i.c.) NT in adrenalectomized rats. A significant reduction of serum levels of TSH, PRL and GH following i.c. NT (30 micrograms) was observed after 2h of CRS. The gastrosecretory studies revealed that i.c. NT (30 micrograms) did not affect gastric acid secretion in pylorus ligated rats. However, blockade of peripheral (gut) cholinergic (muscarinic) receptors with i.p. atropine methylbromide (1 mg/kg) significantly raised gastric pH and reduced gastric acid concentration and output. In conclusion, the results of this study indicate that the acute protective effect of brain NT appears to be mediated, at least in part, by the sympathoadrenomedullary axis, and not by the pituitary gland or substances derived from the pituitary or by inhibition of gastric acid secretion.

Adrenalectomy↗
PubMed1987

GABA uptake is inhibited by thyroid hormones: implications for depression.

Studies of the effects of thyroid hormones on the uptake of neurotransmitters by homogenates of rat cerebral cortex have revealed a significant competitive inhibition of neuronal uptake of [3H]GABA by thyroid hormones (T3 greater than T4 greater than rT3). The IC50 for inhibition of GABA uptake by T3 was estimated at 4 microM and that of T4 at 11 microns. GABA uptake in homogenates of cerebral cortex from hypothyroid rats was significantly enhanced over that of controls; however, uptake in tissues from hyperthyroid rats was not significantly diminished.

Animals↗
PubMed1987

The effects of thyroid state on beta-adrenergic and serotonergic receptors in rat brain.

The effects of hyperthyroidism or hypothyroidism, alone or in combination with the tricyclic antidepressant desmethylimipramine (DMI), on brain beta-adrenergic and serotonin (5HT2) receptors were studied in adult male Sprague-Dawley rats. Intraperitoneal administration of T3 or T4 for 7 days increased the number of cortical beta-adrenergic and 5HT2 receptors. These increases were significant at levels of 250 micrograms/kg or above for both hormones. Neither thyroidectomy nor "reverse" T3 (rT3) (500 micrograms/kg) produced an effect on either receptor type. The down-regulation of beta-adrenergic receptors produced by daily subcutaneous injections of 20 mg/kg of DMI for 7 days was partially offset by concurrent administration of T4, whereas the down-regulation of 5HT2 receptors produced by the drug was not affected by concurrent administration of either T3 or T4. Hypothyroidism (thyroidectomy) did not significantly affect the adaptation of these receptor populations to DMI. As regards brain regions other than cortex, T4 (250 micrograms/kg) produced the same changes in hippocampus as in cortex, while thyroidectomy decreased beta-adrenergic receptors only in the cerebellum. Thyroxine also elevated 5HT2 receptors in the hippocampus; thyroidectomy caused a significant decrease in 5HT2 receptors in the striatum.

Animals↗
PubMed1987

Modulation of gamma-aminobutyric acid uptake of rat brain synaptosomes by thyroid hormones.

The effects of thyroid hormones on gamma-aminobutyric acid (GABA) uptake were compared in homogenates and purified synaptosomes from rat cerebral cortex. L-triiodothyronine (T3) and L-thyroxine (T4), but not reverse T3(rT3), blocked GABA uptake in homogenates when hormone and labeled GABA were added to the system simultaneously. Similar effects were obtained when homogenates were preincubated with hormone and washed to remove free hormone before addition of GABA. A competitive inhibitor of neuronal GABA uptake, diaminobutyric acid (DABA), blocked GABA uptake when added with GABA, but not after preincubation and washing. In purified synaptosomes, T3, T4, and rT3 blocked GABA uptake when added simultaneously with GABA and also after preincubation and washing before addition of GABA, thus indicating that binding of hormones had occurred. Other experiments suggested that hormone binding was not at the GABA recognition site and that the effect of T4 was not dependent on conversion to T3.

Animals↗
PubMed1986

Is there paradoxical growth hormone response to thyrotropin-releasing hormone in depression?

Several investigators have reported a paradoxical growth hormone (GH) response to thyrotropin-releasing hormone (TRH) in depressed patients, but other studies have failed to confirm this. In the present study, the GH response to TRH was studied in depressed patients and normal subjects. The rate of paradoxical GH response to TRH in depression was no different than that observed in control subjects. This was the case whether the data was examined using mean values or using frequency of abnormal responses. Patients with blunted thyrotropin (TSH) responses did not differ in GH release from patients with normal TSH response. A variety of factors may have contributed to the earlier reports of a positive GH response to TRH, including the definition of paradoxical GH release and the fact that depressed patients exhibit more frequent spontaneous diurnal GH release than do normal subjects.

Adult↗
PubMed1986

Effect of dopamine agonists and antagonists on neurotensin-induced antinociception.

In previous reports, we have demonstrated that intracisternal (IC) administration of neurotensin (NT), an endogenous tridecapeptide, produces significant antinociception in a variety of analgesic tests, including the hot-plate test. In addition, many of the central nervous system effects of NT (i.e., hypothermia, gastric cytoprotection) appear to be mediated by brain dopamine (DA) systems. In this study, we evaluated the effect of selected DA agonists and antagonists on NT-induced antinociception in the hot-plate test with mice. Doses, route of administration, and pretreatment interval were determined from the available literature to significantly affect the incidence of DA-dependent behaviors. Pretreatment with chlorpromazine but not haloperidol significantly potentiated NT-induced antinociception. This potentiating effect of chlorpromazine appears not to be due to any intrinsic antinociceptive activity of this agent, chlorpromazine had no significant effect on hot-plate latencies when administered alone. The involvement of DA on NT-induced antinociception was further substantiated by the findings that pretreatment with several DA receptor agonists, including methylphenidate, apomorphine, and d-amphetamine, significantly antagonized the antinociceptive response to IC NT. None of these agents significantly altered the animal's response to the hot-plate when administered alone. The data furnished in the present report suggest that central DA circuits may be involved in the expression of NT-induced antinociception.

Analgesics↗
PubMed1986

Interactive effects of intracisternal oxytocin and other centrally active substances on colonic temperatures of mice.

Oxytocin (OXY) administered intracisternally to adult male mice produced a significant dose-related (1-4 micrograms) increase in colonic temperatures at an ambient temperature of 25 degrees C. The maximal rise in temperature occurred 30 min after administration of the peptide. The interactive effects on colonic temperature of central OXY with equimolar amounts of neurotensin, bombesin or beta-endorphin or of 2 2 mg/kg of chlorpromazine were investigated. OXY significantly antagonized the hypothermia produced by all of these substances. Pretreatment of mice with haloperidol or naloxone failed to prevent OXY-induced hyperthermia. The hyperthermic action of OXY and the interactive effects of OXY with other peptides on thermoregulation may be physiologically significant during parturition and lactation.

Animals↗
PubMed1985

Phospholipid liposomes potentiate the inhibitory effect of antidepressant drugs on immobility of rats in a despair test (constrained swim).

Male rats forced to swim in a cylinder assumed an immobile posture. Immobility was reduced by antidepressant drugs, such as imipramine, desimipramine, iproniazid and mianserin injected 24, 5 and again 1 h prior to behavioral testing. Subchronic (4, 7 and 10 days) treatment with sonicated preparations of bovine hypothalamic phospholipid liposomes potentiated the inhibitory effect of all antidepressant drugs in the despair test. Acute administration of phospholipid liposomes failed to influence the drug effect. Furthermore, neither subchronic nor acute administration of phospholipid liposomes per se modified the immobility in the despair test. It is possible that the action of phospholipid liposomes on the inhibitory effect of antidepressant drugs on immobility of rats in the despair test may depend on potentiation of antidepressant-induced change in the sensitivity of monoamine receptors in the brain.

Animals↗
PubMed1985

Effects of intrahypothalamic injection of quinolinic acid on anterior pituitary hormone secretion in the unanesthetized rat.

Bilateral intrahypothalamic injections of the brain metabolite quinolinic acid (QUIN) were made in an attempt to examine its effects on the secretion of LH, PRL, GH and TSH. Quin, a neuroexcitatory amino acid with close structural similarities to glutamate, kainate and N-methylaspartate, was infused into unanesthetized male rats, the animals sacrificed 7.5 min later, and serum hormone concentrations determined by radioimmunoassay. QUIN caused surges in LH, PRL and GH release (316, 607 and 1,134% of control, respectively, at 50 micrograms QUIN) without affecting the serum concentrations of TSH. At lower doses, a preferential effect of QUIN on PRL release was observed. All QUIN-induced hormonal changes were inhibited by concomitant administration of the specific antagonist (-)-2-amino-7-phosphonoheptanoic acid, indicating the presence of QUIN-sensitive receptors on neurons which are intimately associated with endocrine regulation. Moreover, because QUIN-treated animals exhibited behavioral signs of seizure activity and neuroendocrine dysfunction has been reported to occur in human convulsive disorders, the data are also of interest in view of a possible mechanistic link between epileptic phenomena and hormone secretion.

Animals↗
PubMed1985

Effects of chlordecone administration on brain and pituitary peptide systems.

It has been clearly demonstrated that chlordecone exerts estrogen-like effects on the reproductive system. However, the extent to which the estrogenic activity of this neurotoxicant may contribute to its central nervous system effects is not clear. The purpose of this study was to compare the estrogenic activity of chlordecone and estrogen on the rat hypothalamo-pituitary axis (HPA) by using the pituitary enkephalin system as a model. It was found that the enkephalin system of the anterior pituitary is regulated by circulating estrogen. Ovariectomy caused an increase in the pituitary content of enkephalin and this increase was prevented by estrogen treatment. Administration of estrogen reduced the pituitary content of this peptide in intact male rats. Similarly, chlordecone treatment reduced the pituitary content of enkephalin in a manner identical to that of estrogen. A single injection of chlordecone (75 mg/kg; i.p.) caused a delayed decrease in the enkephalin level of the anterior lobe (but not the posterior lobe) of the pituitary. This effect of chlordecone was selective to male rats since the pituitary enkephalin level of females was not altered by such treatment. Levels of other pituitary hormones such as beta-endorphin, vasopressin, etc., were not decreased. Further studies revealed that the similarities between chlordecone and estrogen could be extended to other pituitary hormones. For example, implantation of estrogen or of chlordecone in ovariectomized rats caused similar changes in serum prolactin and luteinizing hormone levels. Thus, this study demonstrates a clear estrogen-like action of chlordecone on the HPA. Moreover, due to the similarity of both estrogen and chlordecone to anti-dopaminergic agents in altering [Met5]-enkephalin levels in both the pituitary and caudate nucleus it is speculated that a dopaminergic mechanism is responsible for their actions on the enkephalin system.

Aging↗
PubMed1983

Effects of excitotoxic amino acids on pituitary hormone secretion in the rat.

The acute effects of administration of 4 excitatory amino acids (n-methyl-DL-aspartic acid (NMA), kainic acid (KA), ibotenic acid (IA) and quinolinic acid (QA] on the serum concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH), growth hormone (GH) and prolactin (PRL) were studied in the rat. NMA-treated rats exhibited increased serum LH and GH concentrations while KA-treated rats-showed increases only in serum GH concentrations. Neither IA nor QA altered adenohypophyseal hormone levels. These endocrine alterations induced by NMA and KA are different from those previously reported after administration of glutamate, another excitatory amino acid. The finding that all of the excitatory amino acids studied did not produce identical effects on anterior pituitary hormone secretion may be due to differential permeability of these substances into the central nervous system or because they act at different subtypes of excitatory amino acid receptors.

Amino Acids↗