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Biomedical subjects

D L Wong

Publications and source records attributed to D L Wong.

At least 73 records · Page 4Linked to original sources
PubMed1985

Regulation of biogenic amine methyltransferases by glucocorticoids via S-adenosylmethionine and its metabolizing enzymes, methionine adenosyltransferase and S-adenosylhomocysteine hydrolase.

This report examines the possibility that glucocorticoids control the degradation of adrenal phenylethanolamine N-methyltransferase and pineal hydroxyindole O-methyltransferase by regulating endogenous concentrations of the cosubstrate, S-adenosylmethionine, via its metabolic enzymes, methionine adenosyltransferase and S-adenosylhomocysteine hydrolase. Assays for these latter enzymes were established and optimized in the adrenal and pineal glands. The effects of hypophysectomy and dexamethasone or ACTH treatment on these enzymes were monitored along with concomitant changes in methyltransferase activity. Hypophysectomy simultaneously decreases methionine adenosyltransferase and S-adenosylhomocysteine hydrolase activity in both tissues. Dexamethasone administration to hypophysectomized animals does not alter either methionine adenosyltransferase activity or S-adenosylhomocysteine hydrolase activity in the adrenal gland. However, it does increase S-adenosylhomocysteine hydrolase activity in the pineal gland. In contrast, ACTH administration restores both enzymes in the adrenal while being ineffective in the pineal. These results suggest that glucocorticoids may be regulating S-adenosylmethionine levels and methyltransferase activity via the metabolic enzymes, methionine adenosyltransferase and S-adenosylhomocysteine hydrolase, but that glucocorticoid control may be both tissue- and drug-specific.

Acetylserotonin O-Methyltransferase↗
PubMed1983

Evidence for multiple receptors mediating fluid secretion in salivary glands of ticks.

Using isolated salivary glands of the ixodid tick Amblyomma hebraeum Koch, we tested the effectiveness of butaclamol and sulpiride in blocking fluid secretion stimulated by a number of agonists. (+)-Butaclamol was a potent inhibitor of dopamine, N-methyldopamine and noradrenaline (Ki congruent to 30-60 nM), but was less effective on ergometrine (Ki congruent to 310 nM). Tranylcypromine-stimulated fluid secretion in the absence and presence of (+)-butaclamol and (+/-)-sulpiride suggested that tranylcypromine's action is mediated through two receptors. (+/-)-Sulpiride, though a rather weak antagonist of ergometrine (Ki congruent to 6150 nM), was ineffectual as a dopamine blocker, indicating distinct receptor sites on this epithelium for dopamine and ergometrine. Both (+)-butaclamol and sulpiride reversed the autoinhibition associated with supramaximal levels of dopamine. Sulpiride also abolished spiperone's potentiation of dopamine. Butaclamol, on the other hand, had no such effect on spiperone's potentiation of dopamine. Finally, although the CNS of ticks contains both dopamine and noradrenaline in quantity (congruent to 650 and congruent to 370 ng . g-1 res respectively), the salivary glands contain far more dopamine than noradrenaline (congruent to 85 and congruent to 6 ng . g-1 respectively). The data support the hypothesis that dopamine is a natural transmitter substance in the tick salivary gland, and that there are distinct receptor sites in the epithelium mediating the actions of catecholamines, ergot alkaloids and butyrophenones. The physiological significance of the ergot alkaloid and butyrophenone sites is not clear.

Animals↗
PubMed1982

Effects of hypophysectomy and dexamethasone administration on central and peripheral S-adenosylmethionine levels.

The effects of hypophysectomy and dexamethasone administration on S-adenosylmethionine (SAM) levels in the adrenal, liver, pineal, and various brain regions were examined to determine the central and peripheral relationships between SAM and glucocorticoids in vivo. A simple and sensitive radioenzymatic assay was developed to measure tissue SAM concentrations following removal of its demethylated metabolite, S-adenosylhomocysteine (SAH), whose presence precludes accurate SAM determinations. Three patterns of SAM control emerged. In the adrenal, pineal, striatum, and midbrain, SAM levels fell after hypophysectomy and were restored by dexamethasone administration. In the thalamus, hypothalamus, hippocampus, and cerebellum, SAM levels increased after hypophysectomy and were not altered further by dexamethasone administration. In the liver, cortex, septum, and pons-medulla, SAM levels were not affected by either hypophysectomy or dexamethasone administration. These results suggest that multiple controls regulate SAM levels in vivo. The control factors are both highly tissue and region specific. While glucocorticoids are an important regulatory factor of SAM in some peripheral and CNS tissues, they are not the sole regulatory factor. In CNS regions where hypophysectomy increases SAM levels but glucocorticoid administration does not reverse the effects, other hypothalamic hormones, pituitary hormones, or neural factors may be involved in SAM regulation. Likewise, in regions where neither hypophysectomy nor glucocorticoid administration affects SAM levels, hypothalamic or neural factors may be involved even though pituitary factors do not appear to be important.

Adrenal Glands↗
PubMed1981

Potentiation by spiperone and other butyrophenones of fluid secretion by isolated salivary glands of ixodid ticks.

Isolated salivary glands from the ixodid tick, Amblyomma hebraeum Koch are stimulated to secrete fluid when exposed to dopamine (DA), the maximum response occurring at 10(-6) M. Spiperone, and a number of other butyrophenone derivatives, although lacking intrinsic activity, are able to potentiate the secretion elicited by supramaximal concentrations of DA; this potentiation by spiperone is evident at concentrations in the femtomolar range. Tranylcypromine, a potent, competitive inhibitor of monoamine oxidase (MAO) in tick salivary gland homogenates, has both intrinsic activity and potentiates DA-induced salivation. The fact that spiperone potentiates ergometrine-induced salivation that the prime mechanism of the butyrophenone effect is not by inhibiting catecholamine catabolism. The results also suggest that the receptor for DA and that for butyrophenones are distinct sites. Droperidol, benperidol and bromperidol, all potent neuroleptic drugs, failed (at 10(-9) M) to potentiate salivation. By contrast, R951, R27275 and R1187 (all at 10(-9) M) were very effective potentiators on the salivary gland system, despite the fact that they lack the basic structural requirements for neuroleptic activity. These results suggest that the butyrophenone site in tick salivary glands is different from butyrophenone binding sites in mammalian CNS.

Animals↗
PubMed1980

Regulation of rat pineal hydroxyindole-O-methyltransferase: evidence of S-adenosylmethionine-mediated glucocorticoid control.

Rat pineal hydroxyindole-O-methyltransferase is controlled similarly to adrenal medullary phenylethanolamine N-methyltransferase. S-adenosylmethionine (SAM), the in vivo cofactor utilized by the enzyme to convert N-acetylserotonin to melatonin, protects this methyltransferase against tryptic proteolysis in vitro. Furthermore, in vivo studies suggest that the nucleoside itself is controlled by glucocorticoids. Hypophysectomy decreases hydroxyindole-O-methyltransferase levels as compared with control animals, while dexamethasone and SAM administration restore enzyme levels toward control values. In vitro proteolytic studies further demonstrate that, although N-acetylserotonin does not stabilize the enzyme against trypsinization, this substrate acts synergistically with SAM to confer greater stabilization than observed with SAM alone.

Acetylserotonin O-Methyltransferase↗
PubMed1977

The effects of various mammalian sera on attachment efficiency and thymidine incorporation in primary cultures of mouse mammary epithelial cells.

Mammary epithelial cells from 16- to 17-day pregnant BALB/c mice were cultured in various mammalian sera to determine the kind of serum which stimulates optimal attachment efficiency and thymidine incorporation. Of those sera tested, horse, bovine, lamb, goat and fetal bovine provided the highest attachment efficiency, whereas rat, mouse and human gave the lowest. Rabbit serum stimulated the highest thymidine incorporation into TCA-insoluble material with goat and rat providing the lowest. These results suggest that sera which provide the highest attachment efficiency for primary cultures are not the best stimulants of DNA synthesis and show that an inverse relationship exists between cell attachment and thymidine incorporation for any given type of mammalian serum.

Animals↗