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Biomedical subjects

K G Walton

Publications and source records attributed to K G Walton.

35 records · Page 2Linked to original sources

Effects of isoproterenol on the development of beta-adrenergic receptors in brain cell aggregates.

The development of binding sites for the beta-adrenergic receptor antagonist [125I]iodohydroxybenzylpindolol in reaggregate cultures of fetal rat brain has been investigated. beta-Adrenergic receptor density increased rapidly between 6 and 22 days in culture at which time maximal density was attained. When cultures were grown in the presence of the beta-adrenergic receptor agonist isoproterenol, the development of receptors was markedly inhibited. Cultures were also grown for 15 days in the presence of isoproterenol and then for 7-14 days in the absence of isoproterenol. Following the removal of the agonist, binding sites developed, but to only approximately 50% of the density seen in control cultures.

Animals↗

Prenatal and early postnatal beta-adrenergic receptor-mediated increase of cyclic AMP in slices of rat brain.

The levels of cyclic AMP in slices of cerebral cortex and cerebellum from newborn rats were significantly, but transiently, increased by exposure to the beta-adrenergic agonist, isoproterenol. Isobutylmethyxanthine, an inhibitor of phosphodiesterase, enhanced this effect and permitted its detection in cerebral cortex obtained from the prenatal rat. These results are consistent with the possibilities that functional noradrenergic synapses are formed early in the ontogeny of the CNS, and that norepinephrine may exert cyclic AMP-mediated influences on brain development.

1-Methyl-3-isobutylxanthine↗

Effects of alternative transmitter amines on cyclic AMP formation in rat brain tissue.

Aromatic amines and related compounds, some of which are taken up and released from nerve terminals, might act at brain receptors ordinarily stimulated by traditional amine neurotransmitters. Several of these compounds were evaluated for their ability to stimulate or impede synthesis of cyclic AMP in rat striatal homogenates and cortical slices. In contrast to catecholamines, most had no effect, consistent with their possible role as false transmitters.

Amines↗

Inhibition of dopamine-stimulated adenylate cyclase activity by phenoxybenzamine.

Phenoxybenzamine at a concentration of 2 X 10(-6 M) produced half-maximal inhibition of dopamine-stimulated adenylate cyclase activity in homogenates of rat striatum. Inhibition was sharply dependent on time and temperature of preincubation with the inhibitor. When included in the preincubation medium, dopamine was nearly 8 times more effective than norepinephrine at protecting against this inhibition, whereas neither isoproterenol nor methoxamine appeared to protect at all. These results suggest a direct, and possibly irreversible, interaction of phenoxybenzamine with the dopamine-binding component of the adenylate cyclase.

Adenylyl Cyclase Inhibitors↗

Diester derivatives as apomorphine prodrugs.

A series of diesters of apomorphine was synthesized to serve as prodrugs. They were converted in vivo to free apomorphine, which could be detected in the brain. Stereotyped gnawing behavior and unilateral rotation similar to that produced by apomorphine were induced by all of the diesters but the time course of action of the latter was prolonged. The duration of action generally increased with the size of the ester substituent and appeared to correlate inversely with the rate of hydrolysis of the esters by liver extracts. It is concluded that the diesters serve as prodrugs of apomorphine and their prolonged duration is partly explained by a decreasing rate of hydrolysis attributable to increased steric hindrance at the acyl carbon atoms.

Animals↗

Regulation of protein phosphorylation and sodium transport in toad bladder.

It is well established that active sodium-ion transport and water flow across isolated toad bladder are increased by antidiuretic hormone (ADH) and by cAMP. These agents were also observed in previous studies to cause changes in the amount of radioactive phosphate in a specific protein in the toad bladder. This protein, found by SDS-polyacrylamide gel electrophoresis of toad bladder epithelial preparations, had an apparent molecular weight of 49,000 daltons. In the present study, a correlation was found between the ability of a variety of substances to affect the amount of radioactive phosphate in this 40,000-dalton protein and their ability to alter the rate of sodium transport. Thus several agents (ADH, cAMP, theophylline, adenine, prostaglandin E1, and Mn Cl-2) caused a decrease in the amount of radioactive phosphate in the 49,000-dalton protein and also stimulated active sodium transport across the bladder. Conversely, ZnCl-2 produced an increase in the amount of radioactive phosphate in this protein and an inhibition of sodium transport. With each of these agents, the time-course of change in phosphorylation of this protein was, in general, similar to that for sodium transport. A second phosphoprotein, with an apparent molecular weight of about 42,000 daltons, showed changes in parallel with, but less extensive than, those observed in the 49,000 dalton protein. There was no consistent relationship between changes in level of phosphorylation of either in the 49,000- or 42,000- dalton protein and changes in osmotic water permeability. The results are compatible with the possibility that regulation by ADH and by cAMP of sodium transport in the toad bladder epithelium may be mediated through regulation of the amount of phosphate in a specific protein.

Adenine↗

Regulation of phosphorylation of a specific protein in toad-bladder membrane by antidiuretic hormone and cyclic AMP, and its possible relationship to membrane permeability changes.

Phosphorylation of a specific protein was decreased in intact toad bladders by exposure to either antidiuretic hormone or monobutyryl cyclic AMP. The decrease in phosphorylation caused by these agents preceded the change in electrical potential difference (an indicator of the rate of sodium ion transport) observed in response to the same compounds. The addition of cyclic AMP to homogenates of toad bladder led to a decrease in phosphorylation of the same, or a similar, protein. In subcellular fractionation studies, the effect of cyclic AMP on the phosphorylation of this protein was observed in those fractions rich in membrane fragments, but not in the nuclear or cell-sap fractions. These and other results are compatible with the possibility that the regulation by vasopressin and cyclic AMP of sodium and/or water transport in toad bladder may be mediated through regulation of the phosphorylation of this specific protein.

Animals↗

The impact of the transcendental meditation program on government payments to physicians in Quebec.

PURPOSE: This study evaluated whether governmental medical payments in Quebec were affected by the Transcendental Meditation (TM) technique. DESIGN: This retrospective study used a pre- and postintervention design in which government payments for physicians' services were reviewed for 3 years before and up to 7 years after subjects started the technique. Payment data were adjusted for aging and year-specific variation (including inflation) using normative data. No separate control group was used; thus it is impossible to determine whether the changes were caused by the TM program or some other factor. SUBJECTS: A volunteer group of 677 provincial health insurance enrollees was evaluated. The subjects had chosen to practice the TM technique before they were selected to enter the study. The subjects (348 men, 329 women) had diverse occupations. Their average age was 38 years and ranged from 18 to 71 years at the start of the TM program. INTERVENTION: The TM technique of Maharishi Mahesh Yogi is a standardized procedure practiced for 15 to 20 minutes twice daily while sitting comfortably with eyes closed. SETTING: Province of Quebec, Canada. RESULTS: During the 3 years before starting the TM program, the adjusted payments to physicians for treating the subjects did not change significantly. After beginning TM practice, subjects' adjusted expenses declined significantly. The several methods used to assess the rate of decline showed estimates ranging from 5% to 7% annually. CONCLUSIONS: The results suggests that the TM technique reduces government payments to physicians. However, because of the sampling method used, the generalizability of these results to wider populations could not be evaluated.

Adolescent↗